Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival.
Here, comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced colorectal carcinoma underwent next-generation sequencing via MSK-IMPACT, and a subset of case samples was subjected to high-resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) colorectal carcinoma data. Of the colorectal carcinoma patients sequenced (n= 401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification. In both the MSK-IMPACT and TCGA datasets, BCL2L1 was the most frequently amplified 20q oncogene. However, SRC was the only recognized 20q oncogene with a significant inverse relationship between mRNA upregulation and RAS/RAF mutation (OR, -0.4 ± 0.2,P= 0.02). In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS (P< 0.001) and BRAF (P= 0.01), microsatellite stability (P< 0.001), distal primary tumors (P< 0.001), and mutant TP53 (P< 0.001), but not stage. On multivariate analysis, longer overall survival from the date of metastasis was observed with chromosome 20q gain (P= 0.02) or amplification (P= 0.04) compared with diploid 20q.Implications:20q amplification defines a subset of colorectal cancer patients with better overall survival from the date of metastasis, and further studies are warranted to assess whether the inhibition of 20q oncogenes, such as SRC, may benefit this subset of patients.Mol Cancer Res; 15(6); 708-13. ©2017 AACR.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Ryan N
RN
Ptashkin
Department of Pathology, Columbia University Medical Center, New York, New York.
Carlos
C
Pagan
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Rona
R
Yaeger
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Sumit
S
Middha
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Jinru
J
Shia
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Kevin P
KP
O'Rourke
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Michael F
MF
Berger
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Lu
L
Wang
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Robert
R
Cimera
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Jiajing
J
Wang
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
David S
DS
Klimstra
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Leonard
L
Saltz
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Marc
M
Ladanyi
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Ahmet
A
Zehir
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. hechtmaj@mskcc.org.
Jaclyn F
JF
Hechtman
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000068818:Cetuximab / Q000627:therapeutic use; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation; D000077544:Panitumumab; D016016:Proportional Hazards Models; D016019:Survival Analysis; D048490:raf Kinases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D048490:raf Kinases; D018631:ras Proteins; D000068818:Cetuximab