Ptashkin Ryan N, Pagan Carlos, Yaeger Rona, Middha Sumit, Shia Jinru, O'Rourke Kevin P, Berger Michael F, Wang Lu, Cimera Robert, Wang Jiajing, Klimstra David S, Saltz Leonard, Ladanyi Marc, Zehir Ahmet, Hechtman Jaclyn F
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology, Columbia University Medical Center, New York, New York.
Mol Cancer Res. 2017 Jun;15(6):708-713. doi: 10.1158/1541-7786.MCR-16-0352. Epub 2017 Feb 9.
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 ( = 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, = 0.02). In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS ( < 0.001) and BRAF ( = 0.01), microsatellite stability ( < 0.001), distal primary tumors ( < 0.001), and mutant TP53 ( < 0.001), but not stage. On multivariate analysis, longer overall survival from the date of metastasis was observed with chromosome 20q gain ( = 0.02) or amplification ( = 0.04) compared with diploid 20q. 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. .
在此，对存在20号染色体长臂扩增的结直肠癌的分子和临床特征进行了全面分析。晚期结直肠癌患者的肿瘤和正常DNA通过MSK-IMPACT进行了二代测序，并且一部分病例样本进行了高分辨率微阵列分析（Oncoscan）。利用癌症基因组图谱（TCGA）结直肠癌数据评估了基因组拷贝数与转录本表达之间的关系。在通过MSK-IMPACT测序的401例结直肠癌患者中，148例（37%）存在20号染色体长臂增加，30例（7%）存在20号染色体长臂扩增。在MSK-IMPACT和TCGA数据集中，BCL2L1是20号染色体长臂上最常扩增的癌基因。然而，SRC是唯一被认可的20号染色体长臂癌基因，其mRNA上调与RAS/RAF突变之间存在显著的负相关（OR，-0.4±0.2，P=0.02）。与20号染色体长臂二倍体的结直肠癌相比，20号染色体长臂增加/扩增与野生型KRAS（P<0.001）、BRAF（P=0.01）、微卫星稳定性（P<0.001）、远端原发性肿瘤（P<0.001）和突变型TP53（P<0.001）相关，但与分期无关。多因素分析显示，与20号染色体长臂二倍体相比，20号染色体长臂增加（P=0.02）或扩增（P=0.04）的患者自转移之日起总生存期更长。20号染色体长臂扩增定义了一部分自转移之日起总生存期较好的结直肠癌患者，有必要进一步研究评估抑制20号染色体长臂癌基因（如SRC）是否可能使这部分患者获益。
