Mutant Driver Genes Predict for Survival in Pancreatic Cancer

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Previous genome-sequencing studies found that pancreatic cancer progression depends on 4 main driver genes — KRAS, CDKN2A, SMAD4, and TP53 — but there is a lack of research investigating the effect of
Previous genome-sequencing studies found that pancreatic cancer progression depends on 4 main driver genes — KRAS, CDKN2A, SMAD4, and TP53 — but there is a lack of research investigating the effect of

Mutant driver genes may affect pancreatic cancer prognosis, according to a study published in JAMA Oncology.1

Previous genome-sequencing studies found that pancreatic cancer progression depends on 4 main driver genes — KRAS, CDKN2A, SMAD4, and TP53 — but there is a lack of research investigating the effect of these mutations on patient outcomes.

For this study, researchers assessed the outcomes of 356 patients with resected pancreatic cancer who had alterations on 1 of the 4 main genes determined by immunohistochemistry and next-generation sequencing. The primary outcomes were overall survival (OS) and disease-free survival (DFS).

Patients with KRAS-mutant tumors had a worse median DFS (12.3 months) and OS (20.3 months) compared with patients with wild-type KRAS malignancies (DFS, 16.2 months; OS, 38.6 months). The 5-year OS in mutant-KRAS vs wild-type KRAS was 13.0% vs 30.2%, respectively. Patients with KRAS G12D–mutant tumors had particularly poor outcomes, with median OS of 15.3 months.

The median DFS among patients with tumors lacking CDKN2A vs tumors expressing CDKN2A was 11.5 months vs 14.8 months, respectively; the median OS was 19.7 months vs 24.6 months, respectively.

SMAD4-status did not affect OS or DFS outcomes; altered TP53 was associated only with a shortened DFS (hazard ratio [HR], 1.33; 95% CI, 1.02-1.75; P = .04).

The number of driver gene mutations correlated with DFS and OS outcomes: patients with 4 gene mutations had worse DFS (HR, 1.79; 95% CI, 1.24-2.59; P = .002) and OS (HR, 1.39; 95% CI, 0.98-1.94; P = .06) compared with patients who had 0 to 2 alterations. Patients with 0 to 2 gene mutations, 3 mutations, or 4 mutations had 5-year OS rates of 18.4%, 14.1%, and 8.2%, respectively.

Reference

  1. Qian ZR, Rubinson DA, Nowak JA, et al. Association of alternations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma. JAMA Oncol. 2017 Nov 2. doi: 10.1001/jamaoncol.2017.3420 [Epub ahead of print]

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