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Genetics Faculty

Charis Eng
Professor/Vice Chair
Ph.D. Training Faculty
Genomic Medicine Institute
Lerner Research Institute
Cleveland Clinic NE50
9500 Euclid Avenue
Cleveland, Ohio 44195
Tel: (216) 444-3440
Fax: (216) 636-0655

About Charis Eng

Charis Eng, MD, PhD is the Chair and founding Director of the Genomic Medicine Institute of the Cleveland Clinic, founding Director and attending clinical cancer geneticist of the institute's clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairman of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine. She holds a joint appointment as Professor of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and is a member of Cleveland Clinic's Taussig Cancer Center and of the CASE Comprehensive Cancer Center. Dr. Eng was honored with the Sondra J. and Stephen R. Hardis Endowed Chair in Cancer Genomic Medicine in 2008 and the American Cancer Society Clinical Research Professorship in 2009. In 2010, she was elected to the National Academy of Medicine [then Institute of Medicine (IOM)] of the US National Academies. She continues to hold an honorary appointment at the University of Cambridge. Dr. Eng's research interests may be broadly characterized as clinical cancer genetics translational research. Her work on RET testing in multiple endocrine neoplasia type 2 and characterization of the widening clinical spectra of PTEN mutations have been acknowledged as the paradigm for the practice of clinical cancer genetics, and an important scientific basis for precision oncology. At the clinical interface, Dr. Eng is acknowledged as one of the rare "go to" people on what is and how to implement genetic- and -omics-informed personalized healthcare.

Dr. Eng grew up in Singapore and Bristol, UK and entered the University of Chicago at the age of 16. After completing an MD and PhD at its Pritzker School of Medicine, she specialized in internal medicine at Beth Israel Hospital, Boston and trained in medical oncology at Harvard's Dana-Farber Cancer Institute. She was formally trained in clinical cancer genetics at the University of Cambridge and the Royal Marsden NHS Trust, UK, and in laboratory-based human cancer genetics by Prof Sir Bruce Ponder. At the end of 1995, Dr. Eng returned to the Farber as Assistant Professor of Medicine, and in January, 1999 was recruited by The Ohio State University as Associate Professor of Medicine and Director of the Clinical Cancer Genetics Program. In 2001, she was honored with the conferment of the Davis Professorship and appointed Co-Director of the Division of Human Genetics in the Department of Internal Medicine. In 2002, she was promoted to Professor and Division Director, and was conferred the Klotz Endowed Chair. She was recruited to the Cleveland Clinic in Sept, 2005. Dr. Eng has published over 470 peer reviewed original papers in such journals as the New England Journal of Medicine, JAMA, Lancet, Nature Genetics, Nature, Cell and Molecular Cell. She has received numerous awards and honors including election to the American Society of Clinical Investigation, to the Association of American Physicians and as Fellow of AAAS, the Doris Duke Distinguished Clinical Scientist Award, and named a Local Legend from Ohio bestowed by the American Medical Women's Association in conjunction with the US Senate on women physicians who have demonstrated commitment, originality, innovation and/or creativity in their fields of medicine. Dr. Eng is the 2005 recipient of the ATA Van Meter Award at the 13th International Thyroid Conference, the 2006 Ernst Oppenheimer Award of The Endocrine Society, the 2006 American Cancer Society John Peter Minton, MD, PhD Hero of Hope Research Medal of Honor, the 2014 James Ewing Lecturership of the Society for Surgical Oncology, the 2014 AACR WICR-Charlotte Friend Memorial Lectureship, 2015 and 2017 University of Chicago Medical Alumni Distinguished Service Award and Alumni Professional Achievement Award. She serves as the Editor-in-Chief of Endocrine Related Cancer (2011-2020). She was the North American Editor of the Journal of Medical Genetics (1998-2005), Senior Editor of Cancer Research (2004-09), and Associate Editor of the Journal of Clinical Endocrinology and Metabolism (2005-09) and of the American Journal of Human Genetics (2007-09). Dr. Eng completed a 3-year term on the Board of Directors of the American Society of Human Genetics, has completed a 2-year term as Chair of the Clinical Science Committee of the Personalized Medicine Coalition and a 5-year term on the Board of Scientific Directors of the National Human Genome Research Institute. Dr. Eng was appointed by Kathleen Sebelius to the US Department of Health and Human Services' Secretary's Advisory Committee on Genetics, Health and Society (2009-11). She also served as co-chair of their Task Force to examine whole genome sequencing for clinical application.


The optimal manner of achieving seamless translational cancer research is on a single platform of research, clinical care and education. On such a base, the broad thrust of the Eng laboratory can be characterized as clinical cancer genetics translational research, which involves the utilization and integration of multiple -omics-based platforms to identify, characterize and understand genes which cause susceptibility to high penetrance Mendelian and complex heritable cancers, to determine their role in sporadic carcinogenesis and to perform molecular epidemiologic analyses as they might relate to near-future clinical applications to enable the practice of precision medicine. Upon this framework, we are investigating the following:

Genetic and Functional Characterization of PTEN Hamartoma Tumor Syndrome (PHTS): My lifelong work is to identify, characterize, and understand genes that cause susceptibility to inherited cancer syndromes and to determine how these genes can be used to develop new clinical applications. My independent career began in late 1995, when the heritable hamartoma neoplasias were a mystery and very difficult to recognize clinically and no genetic etiologies had been identified. Leading a multi-national team, we mapped the predisposition gene for Cowden syndrome (CS), a difficult to recognize, under-diagnosed hamartoma syndrome then characterized as having high risks of breast and thyroid cancers, to 10q22-q23. Subsequently, we identified that gene as PTEN, the first time a phosphatase gene was shown to be a cancer-predisposition gene. Shortly thereafter, we also showed that germline PTEN mutations cause a subset of a seemingly clinically disparate (from CS) and rare syndrome called Bannayan-Riley-Ruvalcaba syndrome (BRRS). We have delineated the PTEN mutation spectra in CS and BRRS, adding previously unknown clinical phenotypes such as autism and colonic (mixed) polyposis and colon cancer risk. We also completed multi-national a multi-institutional prospective study to build a clinical risk calculator which predicts a priori probability of a PTEN mutation for easier recognition of these patients for referral to genetics professionals. When we identified PTEN as the Cowden and BRRS predisposition gene, the known malignancy risks were breast and follicular thyroid cancers. We performed a multi-national multi-institutional prospective study to delineate the PTEN-associated neoplasias and lifetime risks. The latter led to adding endometrial, renal and colon cancer and melanoma to the PTEN-clinical phenotypic spectrum. We have also performed a first pass prospective study of second primary malignancies (SMN) in individuals with germline PTEN mutations, showing markedly elevated SMN risks for all associated cancers, especially those of the breast. All these observations have led to more precise cancer risk assessment and clinical management, as well as predictive testing of as yet unaffected family members, which we have shown to be cost-effective as well.

Our current PTEN research foci are three-fold. First, we are investigating genomic and non-genomic modifiers of cancer risk in PHTS. While individuals with PHTS have an 85% lifetime risk of female breast cancer, 35% of thyroid cancer, and so on, it is not possible to accurately predict which single individual will or will not develop a specific cancer. More recently, we have found germline SDHD variants increasing breast cancer risk in those with germline PTEN mutations. Succinate dehydrogenase subunit D is part of mitochondrial complex II, and we have shown that SDHD variants lead to increased ROS and HIF1alpha signaling and destabilization of p53 via non-canonical NQ01 downregulation secondary to NAD/FAD imbalance, leading to apoptosis resistance and oxidative stress. As such, we are currently searching for further modifiers of cancer risk in PHTS utilizing broad genomics, computational biophysics and functional approaches.

Second, we are using PHTS as a model for sporadic thyroid and breast cancer initiation, given that PTEN plays a major somatic role in many sporadic malignancies and that germline mutations are the earliest, hence, initiating event in heritable disease, ie, PHTS. Here, we are interrogating the crosstalk between PTEN and SDHx using genomic, cell (in vitro) and murine models.

Third, although the Eng lab has uncovered several predisposition genes in PTEN mutations PHTS, there remain almost half of CS and CS-like individuals who have no mutations in these known genes. Therefore, we are continuing to search for as yet identified susceptibility genes for CS/CS-like syndromes.

Dissecting the PTEN "Switch" of Developing Cancer versus Autism: Why and how germline mutation in a single gene PTEN results in such disparate phenotypes as cancer and autism is a conundrum. A major thrust of my lab is to determine the mechanistic "switch(s)" which differentiates the two clinical outcomes. Because of the complexity of our overall goal, we will use an interdisciplinary approach. First, we will leverage computational biophysics modeling and bioinformatics approaches. What we find computationally will be structurally validated. Second, we are utilizing genomics and gene expression approaches leveraging our collection of patient materials and our PTEN mouse model of intracellularly mislocalized PTEN. Finally, we will utilize functional, including immunologic, interrogation of cellular and animal models, which will be validated with patient samples.

In order to understand the PTEN "switch," it is important to characterize our PTEN mouse model with autism-like phenotypes. In following our CS/CS-like cohort with PTEN germline mutations, I noted autism amongst many kindreds. We therefore performed a pilot study prospectively accruing individuals, both children and adults, with macrocephaly (a key phenotype in CS/CSL persons) and autism spectrum disorder (ASD). We were surprised to find 3 of the 17 eligible research participants carrying germline PTEN mutations. This observation has been independently replicated multiple times since our first report in 2005. Since then, we have made the first mouse model of inappropriate PTEN intracellular localization with high-functioning autism as phenotype. The cytoplasm-predominant PTEN protein caused cellular hypertrophy limited to the soma and led to increased NG2 cell proliferation and accumulation of glia. The animals also exhibit significant astrogliosis and microglial activation, indicating a neuroinflammatory phenotype. At the signaling level, PTEN(m3m4) mice show brain region-specific differences in Akt activation. The homozygotes have massive megencephaly in parallel with human patients with PTEN mutations, irrespective of autism status: 94% of those with PTEN mutations have macrocephaly. We subsequently compared PTEN-ASD patients (n=17) to idiopathic (non-PTEN) ASD patients with (macro-ASD, n=16) and without macrocephaly (normo-ASD, n=38) and healthy controls (n=14). PTEN-ASD had a high proportion of missense mutations and showed reduced PTEN protein levels. Compared with the other groups, prominent white-matter and cognitive abnormalities were specifically associated with PTEN-ASD patients, with strong reductions in processing speed and working memory. White-matter abnormalities mediated the relationship between PTEN protein reductions and reduced cognitive ability. Processing speed and working memory deficits and white-matter abnormalities may serve as useful features that signal clinicians that PTEN is etiologic and warranting referral to genetics evaluation. Because of our observations in both patients and mouse model, the current thrust of our PTEN-ASD research involves using cell, including stem cell, and mouse models to interrogate the mechanism of neuroinflammation and of white matter abnormalities as well as the role of oligodendroglia versus astrocytes in PTEN-ASD.

Microbiome in Cancer Risk: The microbiome comprises microbial organisms, such as bacteria and fungi, that are found in and on human bodies. Emerging data have shown the microbiome affecting obesity, diabetes and inflammatory bowel disease as well as responses to immune modulation in cancer treatment. We continue to address our hypothesis that the microbiome transduces signals from the environment to our genes. We are therefore studying the microbiome from gut, urine and oral wash as a modifier of cancer and ASD risk in individuals with PHTS, and in those with and without PHTS. In parallel, we are analyzing the microbiome from tumor and non-tumor tissue as well as gut in sporadic solid tumors that are component to PHTS, namely, breast and thyroid cancers. We have already found dysbiosis in the breast tissues and tumors of those with breast cancer compared to those without cancer. We are currently exploring loaded nanoparticles targeting breast cancer dysbiosis in murine models, to be followed by first in human clinical trials should the former be successful.

We are using oropharyngeal/head and neck squamous cell carcinomas (HNSCC) as our high biomass cancer model. Together with collaborator Dr. Mahmoud Ghannoum, we analyzed the bacteriome, mycobiome and metabolome of HNSCC at a time when metagenomic analysis of cancers were non-existent. In a small pilot followed by a large independent validation series of HNSCC, we found that microbiomes of HNSCC tumors were different from their matched non-malignant oral epithelial tissues, and that the diversity of the former was lower than the latter. We found microbiomic differences in the primary tumors belonging to stage I-II compared to those at stage III-IV, and somatic hypermethylation of such genes as MDR1 and RASSF1A. In parallel, we have found clear metabolomic and mycobiomic differences in HNSCC compared to matched normal oral epithelium. We are now poised to analyze the mechanism by which the microbiome, especially of mixed organisms (bacteria and fungi), and its dysbiosis leads to HNSCC genesis.

Selected Publications

Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes.
Smith IN, Thacker S, Jaini R, Eng C
J Biomol Struct Dyn (2018);:1-17
See PubMed abstract

Microbiome in PTEN hamartoma tumor syndrome
Byrd V, Getz T, Padmanabhan R, Arora H, Eng C
Endocr Relat Cancer (2018);25(3):233-243
See PubMed abstract

Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.
Yehia L, Ni Y, Sesock K, Niazi F, Fletcher B, Chen HJL, LaFramboise T, Eng C
PLoS Genet (2018);14(4):e1007352
See PubMed abstract

Bacteriome and mycobiome associations in oral tongue cancer.
Mukherjee PK, Wang H, Retuerto M, Zhang H, Burkey B, Ghannoum MA, Eng C
Oncotarget (2017);8(57):97273-97289
See PubMed abstract

Breast tissue, oral and urinary microbiomes in breast cancer.
Wang H, Altemus J, Niazi F, Green H, Calhoun BC, Sturgis C, Grobmyer SR, Eng C
Oncotarget (2017);8(50):88122-88138
See PubMed abstract

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.
Bausch B, Schiavi F, Ni Y, Welander J, Patocs A, Ngeow J, Wellner U, Malinoc A, Taschin E, Barbon G, Lanza V, Söderkvist P, Stenman A, Larsson C, Svahn F, Chen JL, Marquard J, Fraenkel M, Walter MA, Peczkowska M, Prejbisz A, Jarzab B, Hasse-Lazar K, Petersenn S, Moeller LC, Meyer A, Reisch N, Trupka A, Brase C, Galiano M, Preuss SF, Kwok P, Lendvai N, Berisha G, Makay Ö, Boedeker CC, Weryha G, Racz K, Januszewicz A, Walz MK, Gimm O, Opocher G, Eng C, Neumann HPH
JAMA Oncol (2017);3(9):1204-1212
See PubMed abstract

Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma.
Mukherjee PK, Funchain P, Retuerto M, Jurevic RJ, Fowler N, Burkey B, Eng C, Ghannoum MA
BBA Clin (2017);7:8-15
See PubMed abstract

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.
Fishbein L, Leshchiner I, Walter V, Danilova L, Robertson AG, Johnson AR, Lichtenberg TM, Murray BA, Ghayee HK, Else T, Ling S, Jefferys SR, de Cubas AA, Wenz B, Korpershoek E, Amelio AL, Makowski L, Rathmell WK, Gimenez-Roqueplo AP, Giordano TJ, Asa SL, Tischler AS, Pacak K, Nathanson KL, Wilkerson MD, Akbani R, Ally A, Amar L, Amelio AL, Arachchi H, Asa SL, Auchus RJ, Auman JT, Baertsch R, Balasundaram M, Balu S, Bartsch DK, Baudin E, Bauer T, Beaver A, Benz C, Beroukhim R, Beuschlein F, Bodenheimer T, Boice L, Bowen J, Bowlby R, Brooks D, Carlsen R, Carter S, Cassol CA, Cherniack AD, Chin L, Cho J, Chuah E, Chudamani S, Cope L, Crain D, Curley E, Danilova L, de Cubas AA, de Krijger RR, Demchok JA, Deutschbein T, Dhalla N, Dimmock D, Dinjens WN, Else T, Eng C, Eschbacher J, Fassnacht M, Felau I, Feldman M, Ferguson ML, Fiddes I, Fishbein L, Frazer S, Gabriel SB, Gardner J, Gastier-Foster JM, Gehlenborg N, Gerken M, Getz G, Geurts J, Ghayee HK, Gimenez-Roqueplo AP, Giordano TJ, Goldman M, Graim K, Gupta M, Haan D, Hahner S, Hantel C, Haussler D, Hayes DN, Heiman DI, Hoadley KA, Holt RA, Hoyle AP, Huang M, Hunt B, Hutter CM, Jefferys SR, Johnson AR, Jones SJ, Jones CD, Kasaian K, Kebebew E, Kim J, Kimes P, Knijnenburg T, Korpershoek E, Lander E, Lawrence MS, Lechan R, Lee D, Leraas KM, Lerario A, Leshchiner I, Lichtenberg TM, Lin P, Ling S, Liu J, LiVolsi VA, Lolla L, Lotan Y, Lu Y, Ma Y, Maison N, Makowski L, Mallery D, Mannelli M, Marquard J, Marra MA, Matthew T, Mayo M, Méatchi T, Meng S, Merino MJ, Mete O, Meyerson M, Mieczkowski PA, Mills GB, Moore RA, Morozova O, Morris S, Mose LE, Mungall AJ, Murray BA, Naresh R, Nathanson KL, Newton Y, Ng S, Ni Y, Noble MS, Nwariaku F, Pacak K, Parker JS, Paul E, Penny R, Perou CM, Perou AH, Pihl T, Powers J, Rabaglia J, Radenbaugh A, Ramirez NC, Rao A, Rathmell WK, Riester A, Roach J, Robertson AG, Sadeghi S, Saksena G, Salama S, Saller C, Sandusky G, Sbiera S, Schein JE, Schumacher SE, Shelton C, Shelton T, Sheth M, Shi Y, Shih J, Shmulevich I, Simons JV, Sipahimalani P, Skelly T, Sofia HJ, Sokolov A, Soloway MG, Sougnez C, Stuart J, Sun C, Swatloski T, Tam A, Tan D, Tarnuzzer R, Tarvin K, Thiessen N, Thorne LB, Timmers HJ, Tischler AS, Tse K, Uzunangelov V, van Berkel A, Veluvolu U, Vicha A, Voet D, Waldmann J, Walter V, Wan Y, Wang Z, Wang TS, Weaver J, Weinstein JN, Weismann D, Wenz B, Wilkerson MD, Wise L, Wong T, Wong C, Wu Y, Yang L, Zelinka T, Zenklusen JC, Zhang JJ, Zhang W, Zhu J, Zinzindohoué F, Zmuda E
Cancer Cell (2017);31(2):181-193
See PubMed abstract

Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas.
Wang H, Funchain P, Bebek G, Altemus J, Zhang H, Niazi F, Peterson C, Lee WT, Burkey BB, Eng C
Genome Med (2017);9(1):14
See PubMed abstract

PTEN Hamartoma Tumor Syndrome (PHTS).
Eng C
In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews (2016);http://www.ncbi.nlm.
See PubMed abstract

Cancer-predisposition gene KLLN maintains pericentric H3K9 trimethylation protecting genomic stability.
Nizialek EA, Sankunny M, Niazi F, Eng C
Nucleic Acids Res (2016);44(8):3586-94
See PubMed abstract

Neural transcriptome of constitutional Pten dysfunction in mice and its relevance to human idiopathic autism spectrum disorder.
Tilot AK, Bebek G, Niazi F, Altemus JB, Romigh T, Frazier TW, Eng C
Mol Psychiatry (2016);21(1):118-25
See PubMed abstract

Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer.
Yehia L, Niazi F, Ni Y, Ngeow J, Sankunny M, Liu Z, Wei W, Mester JL, Keri RA, Zhang B, Eng C
Am J Hum Genet (2015);97(5):661-76
See PubMed abstract

Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.
Frazier TW, Embacher R, Tilot AK, Koenig K, Mester J, Eng C
Mol Psychiatry (2015);20(9):1132-8
See PubMed abstract

Detecting Germline PTEN Mutations Among At-Risk Patients With Cancer: An Age- and Sex-Specific Cost-Effectiveness Analysis.
Ngeow J, Liu C, Zhou K, Frick KD, Matchar DB, Eng C
J Clin Oncol (2015);33(23):2537-44
See PubMed abstract

Cowden syndrome-associated germline SDHD variants alter PTEN nuclear translocation through SRC-induced PTEN oxidation.
Yu W, He X, Ni Y, Ngeow J, Eng C
Hum Mol Genet (2015);24(1):142-53
See PubMed abstract

Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production.
Tilot AK, Gaugler MK, Yu Q, Romigh T, Yu W, Miller RH, Frazier TW, Eng C
Hum Mol Genet (2014);23(12):3212-27
See PubMed abstract

Second malignant neoplasms in patients with Cowden syndrome with underlying germline PTEN mutations.
Ngeow J, Stanuch K, Mester JL, Barnholtz-Sloan JS, Eng C
J Clin Oncol (2014);32(17):1818-24
See PubMed abstract

Cognitive characteristics of PTEN hamartoma tumor syndromes.
Busch RM, Chapin JS, Mester J, Ferguson L, Haut JS, Frazier TW, Eng C
Genet Med (2013);15(7):548-53
See PubMed abstract

Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps.
Ngeow J, Heald B, Rybicki LA, Orloff MS, Chen JL, Liu X, Yerian L, Willis J, Lehtonen HJ, Lehtonen R, Mester JL, Moline J, Burke CA, Church J, Aaltonen LA, Eng C
Gastroenterology (2013);144(7):1402-9, 1409.e1-5
See PubMed abstract

Implementation of universal microsatellite instability and immunohistochemistry screening for diagnosing lynch syndrome in a large academic medical center.
Heald B, Plesec T, Liu X, Pai R, Patil D, Moline J, Sharp RR, Burke CA, Kalady MF, Church J, Eng C
J Clin Oncol (2013);31(10):1336-40
See PubMed abstract

Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes.
Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, Eng C
Am J Hum Genet (2013);92(1):76-80
See PubMed abstract

Elevated plasma succinate in PTEN, SDHB, and SDHD mutation-positive individuals.
Hobert JA, Mester JL, Moline J, Eng C
Genet Med (2012);14(6):616-9
See PubMed abstract

Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.
Bebek G, Bennett KL, Funchain P, Campbell R, Seth R, Scharpf J, Burkey B, Eng C
Hum Mol Genet (2012);21(7):1557-65
See PubMed abstract

Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53.
Ni Y, He X, Chen J, Moline J, Mester J, Orloff MS, Ringel MD, Eng C
Hum Mol Genet (2012);21(2):300-10
See PubMed abstract

Lifetime cancer risks in individuals with germline PTEN mutations.
Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C
Clin Cancer Res (2012);18(2):400-7
See PubMed abstract

Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma.
Orloff M, Peterson C, He X, Ganapathi S, Heald B, Yang YR, Bebek G, Romigh T, Song JH, Wu W, David S, Cheng Y, Meltzer SJ, Eng C
JAMA (2011);306(4):410-9
See PubMed abstract

A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing Is Proposed on the Basis of a Prospective Study of 3042 Probands.
Tan MH, Mester J, Peterson C, Yang Y, Chen JL, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C
Am J Hum Genet (2011);88(1):42-56
See PubMed abstract

Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome.
Bennett KL, Mester J, Eng C
JAMA (2010);304(24):2724-31
See PubMed abstract

Frequent Gastrointestinal Polyps and Colorectal Adenocarcinomas in a Prospective Series of PTEN Mutation Carriers.
Heald B, Mester J, Rybicki L, Orloff MS, Burke CA, Eng C
Gastroenterology (2010);139(6):1927-33
See PubMed abstract

Bioethical and clinical dilemmas of direct-to-consumer genomic testing: the problem of misattributed equivalence
Eng C, Sharp RR
Science Transl Med (2010);2: 17cm5

A practical guide to interpretation and clinical application of personal genomic screening
Edelman E, Eng C
Br Med J (2009);339:b4253

Germline and somatic cancer-associated mutations in the ATP-binding motifs of PTEN influence its subcellular localization and tumor suppressive function.
Lobo GP, Waite KA, Planchon SM, Romigh T, Nassif NT, Eng C
Hum Mol Genet (2009);18(15):2851-62
See PubMed abstract

Medullary thyroid cancer: management guidelines of the American Thyroid Association.
Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA
Thyroid (2009);19(6):565-612
See PubMed abstract

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out
Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, 39 others, Cascon A, Opocher G, Ridder GJ, Januszewicz A, Suarez C, Eng C
Cancer Res (2009);69(8):3650-6

Microenvironmental protection in diffuse large-B-cell lymphoma.
Eng C
N Engl J Med (2008);359(22):2379-81
See PubMed abstract

Cancer: A ringleader identified.
Eng C
Nature (2008);455(7215):883-4
See PubMed abstract

Germline Mutations and Variants in the Succinate Dehydrogenase Genes in Cowden and Cowden-like Syndromes.
Ni Y, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, Waite KA, Eng C
Am J Hum Genet (2008);83(2):261-268
See PubMed abstract

SNP arrays in heterogeneous tissue: highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples.
Assié G, LaFramboise T, Platzer P, Bertherat J, Stratakis CA, Eng C
Am J Hum Genet (2008);82(4):903-15
See PubMed abstract

Frequency of germline genomic homozygosity associated with cancer cases.
Assié G, LaFramboise T, Platzer P, Eng C
JAMA (2008);299(12):1437-45
See PubMed abstract

Breast-cancer stromal cells with TP53 mutations and nodal metastases.
Patocs A, Zhang L, Xu Y, Weber F, Caldes T, Mutter GL, Platzer P, Eng C
N Engl J Med (2007);357(25):2543-51
See PubMed abstract

Familial adenomatous polyposis in a patient with unexplained mental retardation.
Heald B, Moran R, Milas M, Burke C, Eng C
Nat Clin Pract Neurol (2007);3(12):694-700
See PubMed abstract

Cowden Syndrome-Affected Patients with PTEN Promoter Mutations Demonstrate Abnormal Protein Translation.
Teresi RE, Zbuk KM, Pezzolesi MG, Waite KA, Eng C
Am J Hum Genet (2007);81(4):756-67
See PubMed abstract

Germline mutations in PTEN and SDHC in a woman with epithelial thyroid cancer and carotid paraganglioma.
Zbuk KM, Patocs A, Shealy A, Sylvester H, Miesfeldt S, Eng C
Nat Clin Pract Oncol (2007);4(10):608-12
See PubMed abstract

Evidence of MEN-2 in the original description of classic pheochromocytoma.
Neumann HP, Vortmeyer A, Schmidt D, Werner M, Erlic Z, Cascon A, Bausch B, Januszewicz A, Eng C
N Engl J Med (2007);357(13):1311-5
See PubMed abstract

Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma.
Fukino K, Shen L, Patocs A, Mutter GL, Eng C
JAMA (2007);297(19):2103-11
See PubMed abstract

Essential role for nuclear PTEN in maintaining chromosomal integrity.
Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, Yin Y
Cell (2007);128(1):157-70
See PubMed abstract

Microenvironmental genomic alterations and clinicopathological behavior in head and neck squamous cell carcinoma.
Weber F, Xu Y, Zhang L, Patocs A, Shen L, Platzer P, Eng C
JAMA (2007);297(2):187-95
See PubMed abstract

Cancer phenomics: RET and PTEN as illustrative models.
Zbuk KM, Eng C
Nat Rev Cancer (2007);7(1):35-45
See PubMed abstract

Nuclear localization of PTEN is regulated by Ca(2+) through a tyrosil phosphorylation-independent conformational modification in major vault protein.
Minaguchi T, Waite KA, Eng C
Cancer Res (2006);66(24):11677-82
See PubMed abstract

Distinct expression profiles of PTEN transcript and its splice variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.
Sarquis MS, Agrawal S, Shen L, Pilarski R, Zhou XP, Eng C.
Am J Hum Genet (2006);79:23-31
See PubMed abstract

PTEN autoregulates its expression by interacting with p53 in a phosphatase-independent manner.
Tang Y, Eng C.
Cancer Res (2006);66:736-42
See PubMed abstract

Total genome analysis of BRCA1/2-related carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation.
Weber F, Shen L, Fukino K, Patocs A, Mutter GL, Caldes T, Eng C.
Am J Hum Genet (2006);78:961-72
See PubMed abstract

downregulates phosphatase and tensin homologue deleted on chromosome ten (PTEN) protein stability partially through caspase-mediated degradation in cells with proteosome dysfunction.
Tang Y, Eng C.
Cancer Res (2006);66:6139-48 p53
See PubMed abstract

Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.
Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, Khoo SK, Patocs A, Martin C, Bridgeman S, Heinz J, Pilarski R, Lehtonen R, Prior TW, Frebourg T, Teh BT, Marchuk DA, Aaltonen LA, Eng C.
JAMA (2005);294:2465-73.
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Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas
Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C.
Nature Genet (2002);32(3):355-7
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Nuclear-cytoplasmic partitioning of PTEN differentially regulates the cell cycle and apoptosis.
Chung JH, Eng C.
Cancer Res (2005);65:8096-8100
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Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import m
Chung JH, Ginn-Pease ME, Eng C.
Cancer Res (2005);65:4108-16
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Genetic classification of benign and malignant thyroid follicular neoplasias based on a 3-gene combination.
Weber F, Shen L, Aldred MA, Morrison CD, Frilling A, Saji M, Schuppert F, Broelsch C, Ringel MD, Eng C.
J Clin Endocrinol Metab (2005);90:2515-21
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Combined total genome loss-of-heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets.
Fukino K, Shen L, Matsumoto S, Morrison CD, Mutter GL, Eng C.
Cancer Res (2004);64:7231-6
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Distinct clinical features characterize paraganglioma syndromes associated with SDHB and SDHD mutations.
Neumann HPH, Pawlu C, Peçzkowska M, Bausch B, McWhinney SR, Muresan M, Buchta M, Franke G, Klisch J, Bley T, Hoegerle S, Boedeker CC, Opocher G, Schipper J, Januszewicz A, Eng C.
JAMA (2004);292:943-51
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Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway.
Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg L, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C.
Am J Hum Genet (2003);73:404-11
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A role for mitochondrial enzymes in inherited neoplasia and beyond.
Eng C, Kiuru M, Fernandez MJ, Aaltonen LA.
Nature Rev Cancer (2003);3:193-202
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Increased nuclear phosphatase and tensin homologue deleted on chromosome 10 is associated with G0G1 in MCF-7 cells
Ginn-Pease ME, Eng C.
Cancer Res (2003);63:282-6
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Germline and somatic PTEN mutations and decreased expression of PTEN protein and dysfunction of the PI3K/Akt pathway in Lhermitte-Duclos disease.
Zhou XP, Marsh DJ, Morrison CD, Maxwell M, Reifenberger G, Eng C.
Am J Hum Genet (2003);73:1191-8
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From developmental disorder to cancer: it's all in the BMP/TGFB family.
Waite KA, Eng C.
Nature Rev Genet (2003);4:763-73
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Germ-line mutations in nonsyndromic pheochromocytoma.
Neumann HPH, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehöfer C, Zerres K, Januszewicz A, Eng C
N Engl J Med (2002);346:1459-66.
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Association of germline mutation in the PTEN tumour suppressor gene and a subset of Proteus sand Proteus-like syndromes.
Zhou XP, Hampel H, Thiele H, Gorlin RJ, Hennekam RCM, Parisi M, Winter RM, Eng C.
Lancet (2001);358:210-1
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Altered PTEN expression as a molecular diagnostic marker for the earliest endometrial precancers.
Mutter GL, Lin M-C, FitzGerald JT, Kum JB, Baak JPA, Lees JA, Weng LP, Eng C.
J Natl Cancer Inst (2000);92:924-31
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Adrenal and extra-adrenal pheochromocytomas in a family with germline RET V804L mutation.
Nilsson O, Tisell L-E, Jansson S, Ahlman H, Gimm O, Eng C.
JAMA (1999);281:1587-8
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Loss-of-function mutations in PPARgamma associated with human colon cancer.
Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Speigelman BM, Eng C
Mol Cell (1999);3:799-804
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PTEN mutation analysis as a molecular diagnostic tool in the inherited hamartoma-cancer syndromes.
Eng C, Peacocke M.
Nature Genet (1998);19:223
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Germline mutations in PTEN are present in Bannayan-Zonana syndrome.
Marsh DJ, Dahia PLM, Zheng Z, Liaw D, Parsons R, Gorlin RJ, Eng C
Nature Genet (1997);16:333-4
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Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.
Liaw D, Marsh DJ, Li J, Dahia PLM, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C*, Parsons R*(*Joint Senior Authors)
Nat Genet. (1997);16(1):64-7
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Genetic testing: the problems and the promise.
Eng C, Vijg J.
Nature Biotechnol (1997);15:422-6
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The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET Mutation Consortium analysis.
Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, Ploos van Amstel HK, Lips CJM, Nishisho I, Takai S-I, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Gharib H, Thibodeau SN, Lacroix A, Frilling A, Ponder BAJ, Mulligan LM
JAMA (1996);276(19):1575-9
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Localization of the gene for Cowden disease to 10q 22-23.
Nelen MR, Padberg GW, Peeters EAJ, Lin A, van den Helm B, Frants RR, Coulon V, Goldstein AM, van Reen MMM, Easton DF, Eeles RA, Hodgson S, Mulvihill JJ, Murday VA, Tucker MA, Mariman ECM, Starink TM, Ponder BAJ, Ropers HH, Kremer H, Longy M, Eng C.
Nature Genet (1996);13(1):114-6
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