Research Summary
Pancreatic cancers: genetics of sporadic and familial pancreatic cancer. In collaboration with the Vogelstein/Kinzler lab, in 2008 we reported exome sequencing for 24 pancreatic cancers, where we confirmed identified genes in another 92 cancers. In Jones 2009, we identified that the partner and localizer of BRCA2 (PALB2) was a familial pancreatic cancer predisposition gene. Using gene mutations in primary cancers and their metastases, we clocked the progression of pancreatic cancer to demonstrate that metastasis is a late event, occurring after 17 years of growth in the primary site. Finally, in Norris et al, we reported a new method of mutagenesis in pancreatic cancer.
Chemotherapy of pancreatic cancer. In Cui et al, we correlated the genetics of pancreatic cancer with responses to various classes of chemotherapy. In Kamiyama, we developed mice that are both immunodeficient and biochemically selectable. After growth of human cancers in these mice, pure cancer cells can be routinely obtained for drug screening.
Novel molecular pathology tools. We wrote software to simulate pyrosequencing (Chen et al), and developed a method (haplotype counting) to overcome the error rate of next-generation sequencing (Debeljak et al).
Lab
The Pathology Molecular Diagnostics Laboratory offers state-of-the-art clinical molecular testing for leukemia, lymphoma, solid tumors, cancer predisposition and a number of hematologic mutations associated with disease. Their tests are based on the latest research-based knowledge and provide initial diagnostic information, detection of residual disease following therapy, and assessment of disease risk for inherited conditions.
The Pathology Cytogenetics Laboratory offers the most advanced clinical cytogenetics testing available for leukemia, lymphoma and solid tumors. The tests provide initial diagnostic information and minimal risidual disease detection following therapy or transplant. Expert results, interpretation and consultation services from these laboratories aid referring physicians, including oncologists, hematologists, pathologists, obstetricians and geneticists, in the appropriate diagnosis and management of their patients.
Core Facility:
Molecular Pathology & Cytogenetics
Selected Publications
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Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 July; 357: 409-413.
Dudley JC, Lin MT, Le DT, Eshleman JR. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016 Feb 15;22(4):813-20.
Cui Y, Brosnan JA, Blackford A, Sur S, Hruban RH, Kinzler KW, Vogelstein B, Maitra A, Diaz LA, Iacobuzio-Donahue CA, and Eshleman JR. Genetically defined subsets of human pancreatic cancer demonstrate unique in vitro chemosensitivity. Clinical Cancer Research, 2012;18:6519-30. [PMC3513499].
Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, and Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008; 321:1801-6. [PMC2848990].
Eshleman JR, Lang EZ, Bowerfind GK, Parsons R, Vogelstein B, Willson JKV, Veigl M, Sedwick WD, and Markowitz S. Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer. Oncogene. 1995; 10:33-7.
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