Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

Publication ,  Journal Article
Lowery, MA; Wong, W; Jordan, EJ; Lee, JW; Kemel, Y; Vijai, J; Mandelker, D; Zehir, A; Capanu, M; Salo-Mullen, E; Arnold, AG; Yu, KH; Tjan, C ...
Published in: J Natl Cancer Inst
October 1, 2018

BACKGROUND: Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. METHODS: Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. RESULTS: PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. CONCLUSIONS: PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

October 1, 2018

Volume

110

Issue

10

Start / End Page

1067 / 1074

Location

United States

Related Subject Headings

  • Pancreatic Neoplasms
  • Pancreas, Exocrine
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Loss of Heterozygosity
  • Kaplan-Meier Estimate
  • Humans
  • Heterozygote
  • Germ-Line Mutation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lowery, M. A., Wong, W., Jordan, E. J., Lee, J. W., Kemel, Y., Vijai, J., … O’Reilly, E. M. (2018). Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. J Natl Cancer Inst, 110(10), 1067–1074. https://doi.org/10.1093/jnci/djy024
Lowery, Maeve A., Winston Wong, Emmet J. Jordan, Jonathan W. Lee, Yelena Kemel, Joseph Vijai, Diana Mandelker, et al. “Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.J Natl Cancer Inst 110, no. 10 (October 1, 2018): 1067–74. https://doi.org/10.1093/jnci/djy024.
Lowery MA, Wong W, Jordan EJ, Lee JW, Kemel Y, Vijai J, et al. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. J Natl Cancer Inst. 2018 Oct 1;110(10):1067–74.
Lowery, Maeve A., et al. “Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.J Natl Cancer Inst, vol. 110, no. 10, Oct. 2018, pp. 1067–74. Pubmed, doi:10.1093/jnci/djy024.
Lowery MA, Wong W, Jordan EJ, Lee JW, Kemel Y, Vijai J, Mandelker D, Zehir A, Capanu M, Salo-Mullen E, Arnold AG, Yu KH, Varghese AM, Kelsen DP, Brenner R, Kaufmann E, Ravichandran V, Mukherjee S, Berger MF, Hyman DM, Klimstra DS, Abou-Alfa GK, Tjan C, Covington C, Maynard H, Allen PJ, Askan G, Leach SD, Iacobuzio-Donahue CA, Robson ME, Offit K, Stadler ZK, O’Reilly EM. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. J Natl Cancer Inst. 2018 Oct 1;110(10):1067–1074.
Journal cover image

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

October 1, 2018

Volume

110

Issue

10

Start / End Page

1067 / 1074

Location

United States

Related Subject Headings

  • Pancreatic Neoplasms
  • Pancreas, Exocrine
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Loss of Heterozygosity
  • Kaplan-Meier Estimate
  • Humans
  • Heterozygote
  • Germ-Line Mutation