Liying Zhang

Molecular Geneticist

Director, Diagnostic Molecular Genetics Laboratory; Associate Director, Molecular Genetic Pathology Fellowship Program

Conditions Treated:

Liying Zhang, MD, PhD

About Me

I am a board-certified clinical molecular geneticist with a special interest in cancer genetics. As Director of the Diagnostic Molecular Genetics Laboratory at Memorial Sloan Kettering, I am responsible for supervising the molecular diagnostic testing for inherited disorders — in particular the inherited forms of breast, ovarian, colorectal, and other types of cancers. The identification of  genetic alterations enables better medical management options that can reduce risk through prevention or early detection. I have led the development and implementation of various new diagnostic genetic tests, including the next-generation sequencing tool MSK-IMPACT, a comprehensive assay for cancer predisposition testing. I am responsible for the molecular oncology tests used for screening of cancer predisposition syndromes, such as Lynch syndrome, and for patient selection in clinical trials. I also oversee strategic planning for the laboratory’s technologies, instrumentation, staffing, budget, and regulatory issues.

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With the availability of high-throughput DNA sequencing technologies, our ability to detect DNA sequence variants has greatly surpassed the ability to interpret their clinical impact. National and international projects have started to address the complexity of interpreting genetic variants. Currently, I am a cancer genetics expert participating in the cancer working group for ClinicGen, one of the leading efforts. I am also a committee member on The BRCA Challenge project organized by UNESCO.  We aim to share the knowledge on genetic variations and develop a framework for evaluating them

As Associate Director of the Molecular Genetics Pathology (MGP) fellowship at MSK, I teach MGP fellows in this ACGME-accredited training program and provide the appropriate academic environment for their growth.

My research has focused on interpretation, classification, and characterization of the sequence variants in cancer predisposition genes such as BRCA1, BRCA2, MLH1, MSH2, MSH6, and CDH1. We use molecular biology, molecular genetics, and biochemical approaches to study how these sequence variants alter the function of the proteins sufficiently to predispose cells to cancer development. I lead ongoing research projects to investigate sequence variants related to hereditary breast, ovarian, gastric, and colon cancers. These research results will provide important information for improved patient management.

  • Clinical Expertise: Diagnostic Molecular Genetics
  • Languages Spoken: English
  • Education: MD, Peking University (China); PhD, The Johns Hopkins University; MS (Bioinformatics), The Johns Hopkins University
  • Fellowships: Memorial Sloan Kettering Cancer Center
  • Board Certifications: Clinical Molecular Genetics

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Osorio A, Milne RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I, de la Hoya M, Duran M, Díez O, Ramón Y Cajal T, Konstantopoulou I, Martínez-Bouzas C, Andrés Conejero R, Soucy P, McGuffog L, Barrowdale D, Lee A, Swe-Brca, Arver B, Rantala J, Loman N, Ehrencrona H, Olopade OI, Beattie MS, Domchek SM, Nathanson K, Rebbeck TR, Arun BK, Karlan BY, Walsh C, Lester J, John EM, Whittemore AS, Daly MB, Southey M, Hopper J, Terry MB, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Hansen TV, Jønson L, Ejlertsen B, Gerdes AM, Infante M, Herráez B, Moreno LT, Weitzel JN, Herzog J, Weeman K, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Bonanni B, Mariette F, Volorio S, Viel A, Varesco L, Papi L, Ottini L, Tibiletti MG, Radice P, Yannoukakos D, Garber J, Ellis S, Frost D, Platte R, Fineberg E, Evans G, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Eccles D, Cook J, Hodgson S, Brewer C, Tischkowitz M, Douglas F, Porteous M, Side L, Walker L, Morrison P, Donaldson A, Kennedy J, Foo C, Godwin AK, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, Meindl A, Ditsch N, Arnold N, Plendl HJ, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Gehrig A, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Damiola F, Poppe B, Claes K, Piedmonte M, Tucker K, Backes F, Rodríguez G, Brewster W, Wakeley K, Rutherford T, Caldés T, Nevanlinna H, Aittomäki K, Rookus MA, van Os TA, van der Kolk L, de Lange JL, Meijers-Heijboer HE, van der Hout AH, van Asperen CJ, Gómez Garcia EB, Hoogerbrugge N, Collée JM, van Deurzen CH, van der Luijt RB, Devilee P, Hebon, Olah E, Lázaro C, Teulé A, Menéndez M, Jakubowska A, Cybulski C, Gronwald J, Lubinski J, Durda K, Jaworska-Bieniek K, Johannsson OT, Maugard C, Montagna M, Tognazzo S, Teixeira MR, Healey S, Investigators K, Olswold C, Guidugli L, Lindor N, Slager S, Szabo CI, Vijai J, Robson M, Kauff N, Zhang L, Rau-Murthy R, Fink-Retter A, Singer CF, Rappaport C, Geschwantler Kaulich D, Pfeiler G, Tea MK, Berger A, Phelan CM, Greene MH, Mai PL, Lejbkowicz F, Andrulis I, Mulligan AM, Glendon G, Toland AE, Bojesen A, Pedersen IS, Sunde L, Thomassen M, Kruse TA, Jensen UB, Friedman E, Laitman Y, Shimon SP, Simard J, Easton DF, Offit K, Couch FJ, Chenevix-Trench G, Antoniou AC, Benitez J.DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers. PLoS Genet. 2014 Apr 3;10(4):e1004256. doi: 10.1371/journal.pgen.1004256. eCollection 2014 Apr. 

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, Martins A, Moller P, Morak M, Nystrom M, Peltomaki P, Pineda M, Qi M, Ramesar R, Rasmussen LJ, Royer-Pokora B, Scott RJ, Sijmons R, Tavtigian SV, Tops CM, Weber T, Wijnen J, Woods MO, Macrae F, Genuardi M; InSiGHT. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHTlocus-specific database. Nat Genet. 2014 Feb;46(2):107-15. doi: 10.1038/ng.2854. Epub 2013 Dec 22. 

Schrader K, Stratton KL, Murali R, Laitman Y, Cavallone Y, Offit L, Wen YH, Thomas T, Shah S, Rau-Murthy R, Manschreck C, Salo-Mullen E, Otegbeye E, Corines M, Zhang L, Norton L, Hudis C, Klein RJ, Kauff N, Robson M, Stadler Z, Haber DA, Lipkin S, Friedman E, Foulkes WD, Altshuler D, Vijai J, Offit K Genome Sequencing of Multiple Primary Tumors Reveals Novel PALB2 Variant.  Journal of Clinical Oncology. In press.

Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O’Reilly R, Manschreck C, Harlan-Fleischut MH, Zhang L, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Offit K, Burdett L, Boulton S, Savage1 SA, and Petrini, JHJ. A Recessive Founder Mutation in Regulator of Telomere Elongation Helicase 1, RTEL1, Underlies Severe Immunodeficiency and Features of Hoyeraal Hreidarsson Syndrome.  PLoS Genetics 2013 Aug;9(8):e1003695.

Shah S, Kim Y, Ostrovnaya I, Murali R, Schrader K, Lach F, Sarrel K, Rau-Murthy R, Hansen N, Zhang L, Kirchhoff T, Stadler Z, Robson M, Vijai J, Offit K and Smogorzewska A SLX4 mutation in hereditary breast cancer PLoS One 2013 Jun 26;8(6):e66961.

Vijai J, Kirchhoff T, Schrader KA, Brown J, Dutra-Clarke AV, Manschreck C, Hansen N, Rau-Murthy R, Sarrel K, Przybylo J, Shah S, Cheguri S, Stadler Z, Zhang L, Paltiel O, Ben-Yehuda D, Viale A, Portlock C, Straus D, Lipkin SM, Lacher M, Robson M, Klein RJ, Zelenetz A, Offit K Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies. PLoS Genetics 2013;9(1):e1003220.

Ren Q, Zhang L*, Ruoff R, Ha S, Wang J, Jain S, Reuter R, Gerald W, Giri DD, Melamed J, Garabedian MJ, Lee P, and Logan SK. Expression of androgen receptor and its phosphorylated forms in breast cancer progression. Cancer. 2013, Jul 15;119(14):2532-40.

Stadler ZK, Salo-Mullen E, Zhang L, Shia J, Bacares R, Power DG, Weiser M, Coit D, Robson ME, Offit K, Schattner M. Juveile Polyposis Syndrome Presenting with Familial Gastric Cancer and Massive Gastric Polyposis. J Clin Oncol. 2012 Jul 23.

Karamurzin Y, Zeng Z, Stadler ZK, Zhang L, Ouansafi I, Al-Amadie HA, Sempous C, Saltz LB, Soslow RA, O’Reilly EM, Paty PD, Coit DG, Shia J, Klimstra DS. Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature.  Hum Pathol. 2012 Apr 17.

Zhang L, Chen L, Bacares R, Ruggeri JM, Somar J, Kemel Y, Stadler ZK, Offit K. BRCA1 R71K missense mutation contributes to cancer predisposition by increasing alternative transcript levels. Breast Cancer Res Treat. 2011, Dec; 130(3): 1051-6 

Shah M, Salo-Mullen E, Stadler Z, Ruggeri J, Mirander M, Pristyazhnyuk Y, Zhang L. De novo CDH1 mutation in a family presenting with early-onset diffuse gastric cancer. Clinical Genetics Jun 11, 2011;

Stadler ZK, Salo-Mullen E, Sabbaghian N, Simon JA, Zhang L, Olson SH, Kurtz R, Offit K, Foulkes WD, Robson ME, Tischkowitz M. Germline PALB2 mutation analysis in breast-pancreas cancer families. J Med Genet 2011.

Zhang L, Fleischut M, Kohut K, Spencer S, Wong K, Stadler Z, Kauff N, Offit K, Robson M.. Assessment of the prevalence of de novo mutations in the BRCA1 and BRCA2 genes. Clinical Genetics Jul 2011; 80(1) :97-8

Zhang L, Altuwaijri S, Deng F, Chen L, Lal P, Korets R, Wenske S, Lilja HG, Chang C, Scher HI, Gerald WL NF-kappaB regulates androgen receptor expression and prostate cancer growth. American Journal of Pathology. 2009 Aug;175(2):489-99

Zhang L, Kirchhoff T, Yee CJ, Offit K A Rapid and Reliable Test for BRCA1 and BRCA2 Founder Mutation Analysis in Paraffin Tissue Using Pyrosequencing Journal of Molecular Diagnostics. 2009 May;11(3):176-81.

Zhang L, Bacares R, Boyar S, Nafa K, Offit K. cDNA Analysis Demonstrates that the BRCA2 Intronic Variant IVS4-12del5 is a Deleterious Mutation. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis. 2009 Apr 26;663(1-2):84-9

Zhang L. Immunohistochemistry versus Microsatellite Instability Testing for Screening Colorectal Cancer Patients at Risk for Hereditary Nonpolyposis Colorectal Cancer Syndrome: Part II. The Utility of Microsatellite Instability Testing. Journal of Molecular Diagnostics. 2008, 10(4):301-7

Doane A, Danso M, Lal P, Donaton M, Zhang L, Hudis C, Gerald WL An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene. 2006, 25:3994-4008

Gao S, Lee P, Wang H, Gerald WL, Adler M, Zhang L, Wang YF, and Wang Z. The androgen receptor directly targets the c-FLIP gene to promote the androgen-independent growth of prostate cancer cells. Molecular Endocrinology. 2005, 19: 1792-1802

Holzbeierlein J, Lal P, LaTulippe E, Smith A, Satagopan J, Zhang L, Ryan C, Smith S, Scher HI, Scardino P, Reuter V, Gerald WL. Comprehensive gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and multiple complimentary mechanisms of therapy resistance. American Journal of Pathology. 2004 164:217-27

Zhang L, Charron M, Wright WW, Chatterjee B, Song CS, Roy AK, Brown TR. Nuclear Factor kappaB Activates Transcription of the Androgen Receptor Gene in Sertoli Cells Isolated from Testes of Adult Rats. Endocrinology. 2004, 145:781-9

Wu X, Ye Y, Zhang L. Graphical Modeling Based Gene Interaction Analysis for Microarray Data. SIGKDD Explorations 2003, 5(2):91-100 (SIGKDD: Special Interest Group on Knowledge Discovery and Datamining; Journal of Association for Computing Machinery)

Morrison A, Chekaluk Y, Bacares R, Ladanyi M, Zhang L. BAP1 Missense Mutation c.2054 A>T (p.E685V) Completely Disrupts Normal Splicing through Creation of a Novel 5’ Splice Site in a Human Mesothelioma Cell Line. PLoS One. 2015, 1;10(4)e0119224 [pmid:25830670]

Zhang L, Xiao A, Ruggeri J, Bacares R, Somar J, Melo S, Figueiredo J, Simões-Correia J, Seruca R, Shah MA. The germline CDH1 c.48 G>C substitution contributes to cancer predisposition through generation of a pro-invasive mutation. Mutat Res. 2014, 770:106-11 [pmid:25771876]

Peterlongo P, Chang-Claude J, Moysich KB, Rudolph A, Schmutzler RK, Simard J, Soucy P, Eeles RA, Easton DF, Hamann U,Wilkening S, Chen B, Rookus MA, Schmidt MK, van der Baan FH, Spurdle AB, Walker LC, Lose F, Maia AT, Montagna M, Matricardi L,Lubinski J, Jakubowska A, Gómez Garcia EB, Olopade OI, Nussbaum RL, Nathanson KL, Domchek SM, Rebbeck TR, Arun BK, Karlan BY, Orsulic S, Lester J, Chung WK, Miron A, Southey MC, Goldgar DE, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Ding YC,Neuhausen SL, Hansen TV, Gerdes AM, Ejlertsen B, Jønson L, Osorio A, Martínez-Bouzas C, Benitez J, Conway EE, Blazer KR,Weitzel JN, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Barile M, Ficarazzi F, Mariette F, Fortuzzi S, Viel A, Giannini G, Papi L,Martayan A, Tibiletti MG, Radice P, Vratimos A, Fostira F, Garber JE, Donaldson A, Brewer C, Foo C, Evans DG, Frost D, Eccles D,Brady A, Cook J, Tischkowitz M, Adlard J, Barwell J, Walker L, Izatt L, Side LE, Kennedy MJ, Rogers MT, Porteous ME, Morrison PJ,Platte R, Davidson R, Hodgson SV, Ellis S, Cole T; EMBRACE, Godwin AK, Claes K, Van Maerken T, Meindl A, Gehrig A, Sutter C,Engel C, Niederacher D, Steinemann D, Plendl H, Kast K, Rhiem K, Ditsch N, Arnold N, Varon-Mateeva R, Wappenschmidt B, Wang-Gohrke S, Bressac-de Paillerets B, Buecher B, Delnatte C, Houdayer C, Stoppa-Lyonnet D, Damiola F, Coupier I, Barjhoux L, Venat-Bouvet L, Golmard L, Boutry-Kryza N, Sinilnikova OM, Caron O, Pujol P, Mazoyer S, Belotti M; GEMO Study Collaborators, Piedmonte M, Friedlander ML, Rodriguez GC, Copeland LJ, de la Hoya M, Segura PP, Nevanlinna H, Aittomäki K, van Os TA, Meijers-Heijboer HE,van der Hout AH, Vreeswijk MP, Hoogerbrugge N, Ausems MG, van Doorn HC, Collée JM; HEBON, Olah E, Diez O, Blanco I, Lazaro C,Brunet J, Feliubadalo L, Cybulski C, Gronwald J, Durda K, Jaworska-Bieniek K, Sukiennicki G, Arason A, Chiquette J, Teixeira MR,Olswold C, Couch FJ, Lindor NM, Wang X, Szabo CI, Offit K, Corines M, Jacobs L, Robson ME, Zhang L, Joseph V, Berger A, Singer CF, Rappaport C, Kaulich DG, Pfeiler G, Tea MK, Phelan CM, Greene MH, Mai PL, Rennert G, Mulligan AM, Glendon G, Tchatchou S,Andrulis IL, Toland AE, Bojesen A, Pedersen IS, Thomassen M, Jensen UB, Laitman Y, Rantala J, von Wachenfeldt A, Ehrencrona H,Askmalm MS, Borg Å, Kuchenbaecker KB, McGuffog L, Barrowdale D, Healey S, Lee A, Pharoah PD, Chenevix-Trench G; KConFab Investigators, Antoniou AC, Friedman E. Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev. 2015, 24(1):308-16 [pmid:25336561]

Ye J, Zhou Y, Weiser MR, Gönen M, Zhang L, Samdani T, Bacares R, DeLair D, Ivelja S, Vakiani E, Klimstra DS, Soslow RA, Shia J. Immunohistochemical detection of ARID1A in colorectal carcinoma: loss of staining is associated with sporadic microsatellite unstable tumors with medullary histology and high TNM stage. Hum Pathol. 2014 45(12):2430-6 [pmid:25311944]

Clinical Trials

Research is integral to our mission at Memorial Sloan Kettering, and clinical trials help us discover better forms of patient care and treatment. For you, this could mean access to a new therapy or therapy combination. Click to see a list of the trials I’m currently leading.

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Clinical Trials Co-Investigated by Liying Zhang