TY - JOUR
T1 - Non-V600BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer
AU - Jones, Jeremy C.
AU - Renfro, Lindsay A.
AU - Al-Shamsi, Humaid O.
AU - Schrock, Alexa B.
AU - Rankin, Andrew
AU - Zhang, Ben Y.
AU - Kasi, Pashtoon M.
AU - Voss, Jesse S.
AU - Leal, Alexis D.
AU - Sun, James
AU - Ross, Jeffrey
AU - Ali, Siraj M.
AU - Hubbard, Joleen M.
AU - Kipp, Benjamin R.
AU - McWilliams, Robert R.
AU - Kopetz, Scott
AU - Wolff, Robert A.
AU - Grothey, Axel
N1 - Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
PY - 2017/8/10
Y1 - 2017/8/10
N2 - Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 (non-V600BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600BRAF mutations in metastatic CRC. We pooled patients in whom non-V600BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600BRAF mutations, compared with cancers with V600E BRAF (V600EBRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with non-V600BRAF-mutant metastatic CRC compared with those with both V600EBRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P <.001). In multivariable analysis, non-V600BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P <.001). Conclusion Non-V600BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.
AB - Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 (non-V600BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600BRAF mutations in metastatic CRC. We pooled patients in whom non-V600BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600BRAF mutations, compared with cancers with V600E BRAF (V600EBRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with non-V600BRAF-mutant metastatic CRC compared with those with both V600EBRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P <.001). In multivariable analysis, non-V600BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P <.001). Conclusion Non-V600BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.
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U2 - 10.1200/JCO.2016.71.4394
DO - 10.1200/JCO.2016.71.4394
M3 - Article
C2 - 28486044
AN - SCOPUS:85028703720
SN - 0732-183X
VL - 35
SP - 2624
EP - 2630
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -