Genomic landscape of pancreatic adenocarcinoma: Does age matter? Journal of Clinical Oncology

Irit Ben-Aharon, Moshe Elkabets, Raphael Pelossof, Kenneth H. Yu, Peter J. Allen, Christine A Iacobuzio-Donahue, Steven D. Leach, Maeve Aine Lowery, Karyn A. Goodman, Eileen Mary O'Reilly

Research output: Contribution to journalArticlepeer-review


250 Background: State-of the art genomic analyses of pancreatic adenocarcinoma (PDAC) has yielded insights into signaling pathways underlying carcinogenesis. PDAC is characterized by substantial genomic heterogeneity. We aimed to determine if early-onset PDAC ( ≤ 55 yrs) displays a distinctive molecular landscape from average-age onset PDAC ( ≥ 70 yrs). Methods: Three distinct datasets of PDAC in age groups ≤ 55 and ≥ 70 years old were analyzed. In the first, patients undergoing treatment at MSKCC were consented for MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) next generation sequencing. The second cohort analyzed was The Cancer Genome Atlas (TCGA) dataset for differences in somatic mutations, gene expression and protein expression. The third dataset was the Australian cohort of PDAC (Waddell et al, Nature, 2015). Clinical data were correlated with genomic analyses. Results: One hundred and eighty-three samples were analyzed, yielding N = 56 patients (pts) aged ≤ 55 years and N = 127 pts aged ≥ 70 years. Several genes known to be associated with carcinogenesis differed in mutation frequency across age groups: SMAD4, MYC and PIK3CA displayed higher mutation rates in younger patients (p < 0.05, table below). Comprehensive analysis by cellular pathways indicated that the PI3Kpathway is further altered in the younger population. Protein expression had different patterns in younger versus older patients. Smoking was more prevalent in the early-onset group in all three cohorts (59% vs. 47%). Survival outcomes revealed no differences between the age groups. Conclusions: This exploratory analysis suggests that there may be somatic gene alterations within the population of early onset PDAC patients that involve unique cellular pathways compared with average onset PDAC. Former studies imply these cellular pathways may play a role in smoking-related PDAC carcinogenesis. Larger genomic datasets are warranted for future analysis to support this observation. Gene Early Onset Average Age Onset KRAS 79% 76% TP53 71% 69% CDKN2A 57% 49% SMAD4 43% 22% MYC 29% 14% PIK3CA 21% 3%
Original languageEnglish
Pages (from-to)250
Number of pages1
JournalJournal of Clinical Oncology
Issue number4_suppl
StatePublished - 2016


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