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Dr. Kenneth Kinzler

Ph.D.
(410) 955-0548 (f)
Kenneth Kinzler
Interests

APC and Other Genetic Alterations in Colon and Rectal Cancer Early Diagnosis of Cancer Experimental Therapeutics for Cancer Genetics of Cancer

Titles

Professor of Oncology
Director, Ludwig Center at Johns Hopkins University

Schools\Degrees

Ph.D., Johns Hopkins University

Training

Fellow in Oncology, The Johns Hopkins University

Research Summary

Dr. Kinzler’s laboratory has focused on the genetics of human cancer. They have identified a variety of genetic mutations that underlie cancer, including mutations of the APC pathway that appear to initiate the majority of colorectal cancers and IDH1/2 mutations that underlying many gliomas. In addition, they have developed a variety of powerful tools for analysis of expression and genetic alterations in cancer. Most recently, they have pioneered integrated whole genome analyses of human cancers through expression, copy number, and mutational analyses of all the coding genes in several human cancer types including colorectal, breast, pancreatic and brain. The identification of genetic differences between normal and tumor tissues provide new therapeutic targets, new opportunities for the early diagnosis of cancer, and important insights into the neoplastic process. 

 

Journal Citations

Bettegowda, C.; Huang, X.; Lin, J.; Cheong, I.; Kohli, M.; Szabo, S.A.; Zhang, X.; Diaz, L.A., Jr.; Velculescu, V.E.; Parmigiani, G.; Kinzler, K.W.; Vogelstein, B.; Zhou, S. The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat Biotechnol. 2006 Nov 19;24:1573-1580.

Chen, S.; Wang, W.; Lee, S.; Nafa, K.; Lee, J.; Romans, K.; Watson, P.; Gruber, S.B.; Euhus, D.; Kinzler, K.W.; Jass, J.; Gallinger, S.; Lindor, N.M.; Casey, G.; Ellis, N.; Giardiello, F.M.; Offit, K.; Parmigiani, G. Prediction of germline mutations and cancer risk in the Lynch syndrome. Jama. 2006 Sep 27;296(12):1479-1487.

Cheong, I.; Huang, X.; Bettegowda, C.; Diaz, L.A., Jr.; Kinzler, K.W.; Zhou, S.; Vogelstein, B. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science. 2006 Nov 24;314(5803):1308-1311.

Cummins, J.M.; He, Y.; Leary, R.J.; Pagliarini, R.; Diaz, L.A., Jr.; Sjoblom, T.; Barad, O.; Bentwich, Z.; Szafranska, A.E.; Labourier, E.; Raymond, C.K.; Roberts, B.S.; Juhl, H.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. The colorectal microRNAome. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3687-3692.

Diehl, F.; Li, M.; He, Y.; Kinzler, K.W.; Vogelstein, B.; Dressman, D. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods. 2006 Jul;3(7):551-559.

Li, M.; Diehl, F.; Dressman, D.; Vogelstein, B.; Kinzler, K.W. BEAMing up for detection and quantification of rare sequence variants. Nat Methods. 2006 Feb;3(2):95-97.

Nanda, A.; Karim, B.; Peng, Z.; Liu, G.; Qiu, W.; Gan, C.; Vogelstein, B.; St Croix, B.; Kinzler, K.W.; Huso, D.L. Tumor endothelial marker 1 (Tem1) functions in the growth and progression of abdominal tumors. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3351-3356.

Papadopoulos, N.; Kinzler, K.W.; Vogelstein, B. The role of companion diagnostics in the development and use of mutation-targeted cancer therapies. Nat Biotechnol. 2006 Aug;24(8):985-995.

Sjoblom, T.; Jones, S.; Wood, L.D.; Parsons, D.W.; Lin, J.; Barber, T.D.; Mandelker, D.; Leary, R.J.; Ptak, J.; Silliman, N.; Szabo, S.; Buckhaults, P.; Farrell, C.; Meeh, P.; Markowitz, S.D.; Willis, J.; Dawson, D.; Willson, J.K.; Gazdar, A.F.; Hartigan, J.; Wu, L.; Liu, C.; Parmigiani, G.; Park, B.H.; Bachman, K.E.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-274.

Wood, L.D.; Calhoun, E.S.; Silliman, N.; Ptak, J.; Szabo, S.; Powell, S.M.; Riggins, G.J.; Wang, T.L.; Yan, H.; Gazdar, A.; Kern, S.E.; Pennacchio, L.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006 Oct;27(10):1060-1061.

Diaz, L.A., Jr.; Foss, C.A.; Thornton, K.; Nimmagadda, S.; Endres, C.J.; Uzuner, O.; Seyler, T.M.; Ulrich, S.D.; Conway, J.; Bettegowda, C.; Agrawal, N.; Cheong, I.; Zhang, X.; Ladenson, P.W.; Vogelstein, B.N.; Mont, M.A.; Zhou, S.; Kinzler, K.W.; Vogelstein, B.; Pomper, M.G. Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT. PLoS One. 2007;2(10):e1007.

Huang, C.H.; Mandelker, D.; Schmidt-Kittler, O.; Samuels, Y.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Gabelli, S.B.; Amzel, L.M. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science. 2007 Dec 14;318(5857):1744-1748.

Lin, J.; Gan, C.M.; Zhang, X.; Jones, S.; Sjoblom, T.; Wood, L.D.; Parsons, D.W.; Papadopoulos, N.; Kinzler, K.W.; Vogelstein, B.; Parmigiani, G.; Velculescu, V.E. A multidimensional analysis of genes mutated in breast and colorectal cancers. Genome Res. 2007 Sep;17(9):1304-1318.

Peters, B.A.; St Croix, B.; Sjoblom, T.; Cummins, J.M.; Silliman, N.; Ptak, J.; Saha, S.; Kinzler, K.W.; Hatzis, C.; Velculescu, V.E. Large-scale identification of novel transcripts in the human genome. Genome Res. 2007 Mar;17(3):287-292.

Wood, L.D.; Parsons, D.W.; Jones, S.; Lin, J.; Sjoblom, T.; Leary, R.J.; Shen, D.; Boca, S.M.; Barber, T.; Ptak, J.; Silliman, N.; Szabo, S.; Dezso, Z.; Ustyanksky, V.; Nikolskaya, T.; Nikolsky, Y.; Karchin, R.; Wilson, P.A.; Kaminker, J.S.; Zhang, Z.; Croshaw, R.; Willis, J.; Dawson, D.; Shipitsin, M.; Willson, J.K.; Sukumar, S.; Polyak, K.; Park, B.H.; Pethiyagoda, C.L.; Pant, P.V.; Ballinger, D.G.; Sparks, A.B.; Hartigan, J.; Smith, D.R.; Suh, E.; Papadopoulos, N.; Buckhaults, P.; Markowitz, S.D.; Parmigiani, G.; Kinzler, K.W.; Velculescu, V.E.; Vogelstein, B. The genomic landscapes of human breast and colorectal cancers. Science. 2007 Nov 16;318(5853):1108-1113.

Barber, T.D.; McManus, K.; Yuen, K.W.; Reis, M.; Parmigiani, G.; Shen, D.; Barrett, I.; Nouhi, Y.; Spencer, F.; Markowitz, S.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Lengauer, C.; Hieter, P. Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3443-3448.

Diehl, F.; Schmidt, K.; Choti, M.A.; Romans, K.; Goodman, S.; Li, M.; Thornton, K.; Agrawal, N.; Sokoll, L.; Szabo, S.A.; Kinzler, K.W.; Vogelstein, B.; Diaz, L.A., Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-990.

Diehl, F.; Schmidt, K.; Durkee, K.H.; Moore, K.J.; Goodman, S.N.; Shuber, A.P.; Kinzler, K.W.; Vogelstein, B. Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology. 2008 Aug;135(2):489-498.

He, Y.; Vogelstein, B.; Velculescu, V.E.; Papadopoulos, N.; Kinzler, K.W. The antisense transcriptomes of human cells. Science. 2008 Dec 19;322(5909):1855-1857.

Jones, S.; Chen, W.D.; Parmigiani, G.; Diehl, F.; Beerenwinkel, N.; Antal, T.; Traulsen, A.; Nowak, M.A.; Siegel, C.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Willis, J.; Markowitz, S.D. Comparative lesion sequencing provides insights into tumor evolution. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4283-4288.

Jones, S.; Zhang, X.; Parsons, D.W.; Lin, J.C.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Kamiyama, H.; Jimeno, A.; Hong, S.M.; Fu, B.; Lin, M.T.; Calhoun, E.S.; Kamiyama, M.; Walter, K.; Nikolskaya, T.; Nikolsky, Y.; Hartigan, J.; Smith, D.R.; Hidalgo, M.; Leach, S.D.; Klein, A.P.; Jaffee, E.M.; Goggins, M.; Maitra, A.; Iacobuzio-Donahue, C.; Eshleman, J.R.; Kern, S.E.; Hruban, R.H.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801-1806.

Leary, R.J.; Lin, J.C.; Cummins, J.; Boca, S.; Wood, L.D.; Parsons, D.W.; Jones, S.; Sjoblom, T.; Park, B.H.; Parsons, R.; Willis, J.; Dawson, D.; Willson, J.K.; Nikolskaya, T.; Nikolsky, Y.; Kopelovich, L.; Papadopoulos, N.; Pennacchio, L.A.; Wang, T.L.; Markowitz, S.D.; Parmigiani, G.; Kinzler, K.W.; Vogelstein, B.; Velculescu, V.E. Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16224-16229.

Parsons, D.W.; Jones, S.; Zhang, X.; Lin, J.C.; Leary, R.J.; Angenendt, P.; Mankoo, P.; Carter, H.; Siu, I.M.; Gallia, G.L.; Olivi, A.; McLendon, R.; Rasheed, B.A.; Keir, S.; Nikolskaya, T.; Nikolsky, Y.; Busam, D.A.; Tekleab, H.; Diaz, L.A., Jr.; Hartigan, J.; Smith, D.R.; Strausberg, R.L.; Marie, S.K.; Shinjo, S.M.; Yan, H.; Riggins, G.J.; Bigner, D.D.; Karchin, R.; Papadopoulos, N.; Parmigiani, G.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008 Sep 26;321(5897):1807-1812.

Blackford, A.; Parmigiani, G.; Kensler, T.W.; Wolfgang, C.; Jones, S.; Zhang, X.; Parsons, D.W.; Lin, J.C.; Leary, R.J.; Eshleman, J.R.; Goggins, M.; Jaffee, E.M.; Iacobuzio-Donahue, C.A.; Maitra, A.; Klein, A.; Cameron, J.L.; Olino, K.; Schulick, R.; Winter, J.; Vogelstein, B.; Velculescu, V.E.; Kinzler, K.W.; Hruban, R.H. Genetic mutations associated with cigarette smoking in pancreatic cancer. Cancer Res. 2009 Apr 15;69(8):3681-3688.

Blackford, A.; Serrano, O.K.; Wolfgang, C.L.; Parmigiani, G.; Jones, S.; Zhang, X.; Parsons, D.W.; Lin, J.C.; Leary, R.J.; Eshleman, J.R.; Goggins, M.; Jaffee, E.M.; Iacobuzio-Donahue, C.A.; Maitra, A.; Cameron, J.L.; Olino, K.; Schulick, R.; Winter, J.; Herman, J.M.; Laheru, D.; Klein, A.P.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E.; Hruban, R.H. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009 Jul 15;15(14):4674-4679.

Carter, H.; Chen, S.; Isik, L.; Tyekucheva, S.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Karchin, R. Cancer-specific high-throughput annotation of somatic mutations: computational prediction of driver missense mutations. Cancer Res. 2009 Aug 15;69(16):6660-6667.

Duncan, C.G.; Leary, R.J.; Lin, J.C.; Cummins, J.; Di, C.; Schaefer, C.F.; Wang, T.L.; Riggins, G.J.; Edwards, J.; Bigner, D.; Kopelovich, L.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E.; Yan, H. Identification of microbial DNA in human cancer. BMC Med Genomics. 2009;2:22.

Guda, K.; Moinova, H.; He, J.; Jamison, O.; Ravi, L.; Natale, L.; Lutterbaugh, J.; Lawrence, E.; Lewis, S.; Willson, J.K.; Lowe, J.B.; Wiesner, G.L.; Parmigiani, G.; Barnholtz-Sloan, J.; Dawson, D.W.; Velculescu, V.E.; Kinzler, K.W.; Papadopoulos, N.; Vogelstein, B.; Willis, J.; Gerken, T.A.; Markowitz, S.D. Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12921-12925.

Jones, S.; Hruban, R.H.; Kamiyama, M.; Borges, M.; Zhang, X.; Parsons, D.W.; Lin, J.C.; Palmisano, E.; Brune, K.; Jaffee, E.M.; Iacobuzio-Donahue, C.A.; Maitra, A.; Parmigiani, G.; Kern, S.E.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Eshleman, J.R.; Goggins, M.; Klein, A.P. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 Apr 10;324(5924):217.

Li, M.; Chen, W.D.; Papadopoulos, N.; Goodman, S.N.; Bjerregaard, N.C.; Laurberg, S.; Levin, B.; Juhl, H.; Arber, N.; Moinova, H.; Durkee, K.; Schmidt, K.; He, Y.; Diehl, F.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr.; Kinzler, K.W.; Markowitz, S.D.; Vogelstein, B. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009 Sep;27(9):858-863.

Mandelker, D.; Gabelli, S.B.; Schmidt-Kittler, O.; Zhu, J.; Cheong, I.; Huang, C.H.; Kinzler, K.W.; Vogelstein, B.; Amzel, L.M. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-17001.

Parmigiani, G.; Boca, S.; Lin, J.; Kinzler, K.W.; Velculescu, V.; Vogelstein, B. Design and analysis issues in genome-wide somatic mutation studies of cancer. Genomics. 2009 Jan;93(1):17-21.

Sur, S.; Pagliarini, R.; Bunz, F.; Rago, C.; Diaz, L.A., Jr.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53. Proc Natl Acad Sci U S A. 2009;106(10):3964-3969.

Yan, H.; Parsons, D.W.; Jin, G.; McLendon, R.; Rasheed, B.A.; Yuan, W.; Kos, I.; Batinic-Haberle, I.; Jones, S.; Riggins, G.J.; Friedman, H.; Friedman, A.; Reardon, D.; Herndon, J.; Kinzler, K.W.; Velculescu, V.E.; Vogelstein, B.; Bigner, D.D. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-773.

Yun, J.; Rago, C.; Cheong, I.; Pagliarini, R.; Angenendt, P.; Rajagopalan, H.; Schmidt, K.; Willson, J.K.; Markowitz, S.; Zhou, S.; Diaz, L.A., Jr.; Velculescu, V.E.; Lengauer, C.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009 Sep 18;325(5947):1555-1559.

Boca, S.M.; Kinzler, K.; Velculescu, V.E.; Vogelstein, B.; Parmigiani, G. Patient-oriented gene set analysis for cancer mutation data. Genome Biol. 2010 Nov 23;11(11):R112

Bozic, I.; Antal, T.; Ohtsuki, H.; Carter, H.; Kim, D.; Chen, S.; Karchin, R.; Kinzler, K.W.; Vogelstein, B.; Nowak, M.A. Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18545-18550.

Ericson, K.; Gan, C.; Cheong, I.; Rago, C.; Samuels, Y.; Velculescu, V.E.; Kinzler, K.W.; Huso, D.L.; Vogelstein, B.; Papadopoulos, N. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2598-2603.

He, Y.; Wu, J.; Dressman, D.C.; Iacobuzio-Donahue, C.; Markowitz, S.D.; Velculescu, V.E.; Diaz, L.A., Jr.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010 Mar 25;464(7288):610-614.

Jones, S.; Wang, T.L.; Shih Ie, M.; Mao, T.L.; Nakayama, K.; Roden, R.; Glas, R.; Slamon, D.; Diaz, L.A., Jr.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E.; Papadopoulos, N. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010 Oct 8;330(6001):228-231.

Leary, R.J.; Kinde, I.; Diehl, F.; Schmidt, K.; Clouser, C.; Duncan, C.; Antipova, A.; Lee, C.; McKernan, K.; De La Vega, F.M.; Kinzler, K.W.; Vogelstein, B.; Diaz, L.A., Jr.; Velculescu, V.E. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med. 2010 Feb 24;2(20):20ra14.

Parsons, D.W.; Li, M.; Zhang, X.; Jones, S.; Leary, R.J.; Lin, J.C.; Boca, S.M.; Carter, H.; Samayoa, J.; Bettegowda, C.; Gallia, G.L.; Jallo, G.I.; Binder, Z.A.; Nikolsky, Y.; Hartigan, J.; Smith, D.R.; Gerhard, D.S.; Fults, D.W.; Vandenberg, S.; Berger, M.S.; Marie, S.K.; Shinjo, S.M.; Clara, C.; Phillips, P.C.; Minturn, J.E.; Biegel, J.A.; Judkins, A.R.; Resnick, A.C.; Storm, P.B.; Curran, T.; He, Y.; Rasheed, B.A.; Friedman, H.S.; Keir, S.T.; McLendon, R.; Northcott, P.A.; Taylor, M.D.; Burger, P.C.; Riggins, G.J.; Karchin, R.; Parmigiani, G.; Bigner, D.D.; Yan, H.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. The Genetic Landscape of the Childhood Cancer Medulloblastoma. Science. 2010 Dec 16.

Schmidt-Kittler, O.; Zhu, J.; Yang, J.; Liu, G.; Hendricks, W.; Lengauer, C.; Gabelli, S.B.; Kinzler, K.W.; Vogelstein, B.; Huso, D.L.; Zhou, S. PI3Kalpha Inhibitors That Inhibit Metastasis. Oncotarget. 2010 Sep 1;1(5):339-348.

Yachida, S.; Jones, S.; Bozic, I.; Antal, T.; Leary, R.; Fu, B.; Kamiyama, M.; Hruban, R.H.; Eshleman, J.R.; Nowak, M.A.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Iacobuzio-Donahue, C.A. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010 Oct 28;467(7319):1114-1117.

Jiao, Y.; Shi, C.; Edil, B.H.; de Wilde, R.F.; Klimstra, D.S.; Maitra, A.; Schulick, R.D.; Tang, L.H.; Wolfgang, C.L.; Choti, M.A.; Velculescu, V.E.; Diaz, L.A., Jr.; Vogelstein, B.; Kinzler, K.W.; Hruban, R.H.; Papadopoulos, N. DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Science. 2011 Jan 20;In Press.

 

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