TY - JOUR
T1 - Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma
AU - Yousef, Abdelrahman
AU - Yousef, Mahmoud
AU - Chowdhury, Saikat
AU - Abdilleh, Kawther
AU - Knafl, Mark
AU - Edelkamp, Paul
AU - Alfaro-Munoz, Kristin
AU - Chacko, Ray
AU - Peterson, Jennifer
AU - Smaglo, Brandon G.
AU - Wolff, Robert A.
AU - Pant, Shubham
AU - Lee, Michael S.
AU - Willis, Jason
AU - Overman, Michael
AU - Doss, Sudheer
AU - Matrisian, Lynn
AU - Hurd, Mark W.
AU - Snyder, Rebecca
AU - Katz, Matthew H.G.
AU - Wang, Huamin
AU - Maitra, Anirban
AU - Shen, John Paul
AU - Zhao, Dan
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n = 408).
AB - The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2–3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3–2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2–2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05–2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN’s Know Your Tumor® dataset, n = 408).
UR - http://www.scopus.com/inward/record.url?scp=85184254762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85184254762&partnerID=8YFLogxK
U2 - 10.1038/s41698-024-00505-0
DO - 10.1038/s41698-024-00505-0
M3 - Article
C2 - 38310130
AN - SCOPUS:85184254762
SN - 2397-768X
VL - 8
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
ER -