Abstract | BACKGROUND: METHODS: To assess the frequencies of druggable gene alterations and investigate new potential therapeutic targetable genomic alterations, advanced PC and BTC patients were tested with comprehensive genomic profiling at Foundation Medicine during the course of clinical care. RESULTS: A total of 16 913 PC patients and 3031 BTC patients were available for analyses, and frequencies of genomic alterations were stratified by age (≥40 years or <40 years), microsatellite instability status, tumor mutational burden status (high ≥10 or low <10 Muts/Mb), and select genomic alterations. Alterations in BRCA2, BRAF, ERBB2, CDK12, PIK3CA, FGFR2, EGFR, and other potential targets were seen across cohorts, with enrichment observed within particular subsets such as in PC patients lacking a KRAS mutation. In BTC patients, the rate of ERBB2 amplification was statistically significantly higher in the tumor mutational burden-high population (23.3% vs 13.7%). Interestingly, CDK12 rearrangement was observed in BTC patients with ERBB2 amplification tumors. In patients younger than 40 years, FGFR2 rearrangement (4%) was observed in PC: GATA6 amplification (11.1%) and rearrangement of BRAF (2.8%)FGFR2 (5.6%) was observed in BTC patients. CONCLUSIONS: We identified an appreciable frequency of immunotherapy biomarkers and targetable gene alterations in both PC and BTC, with notable frequencies in PC samples lacking KRAS mutations and children or adolescent and young adult populations, that should encourage comprehensive genomic profiling testing.
|
Authors | Kumiko Umemoto, Hiroyuki Yamamoto, Ritsuko Oikawa, Hiroyuki Takeda, Ayako Doi, Yoshiki Horie, Hiroyuki Arai, Takashi Ogura, Takuro Mizukami, Naoki Izawa, Jay A Moore, Ethan S Sokol, Yu Sunakawa |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 114
Issue 9
Pg. 1279-1286
(09 09 2022)
ISSN: 1460-2105 [Electronic] United States |
PMID | 35583261
(Publication Type: Journal Article)
|
Copyright | © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]. |
Chemical References |
- Biomarkers, Tumor
- Proto-Oncogene Proteins B-raf
- Proto-Oncogene Proteins p21(ras)
|
Topics |
- Adolescent
- Adult
- Biomarkers, Tumor
(genetics)
- Child
- Gastrointestinal Neoplasms
- Genomics
- Humans
- Mutation
- Pancreatic Neoplasms
- Proto-Oncogene Proteins B-raf
(genetics)
- Proto-Oncogene Proteins p21(ras)
(genetics)
- Young Adult
- Pancreatic Neoplasms
|