Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival.
Chromosome 20q Amplification Defines a Subtype of Microsatellite Stable, Left-Sided Colon Cancers with Wild-type RAS/RAF and Better Overall Survival.
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DOI：
10.1158/1541-7786.mcr-16-0352
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
Hechtman JF
中科院分区：
文献类型：
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作者：
Ptashkin RN;Pagan C;Yaeger R;Middha S;Shia J;O'Rourke KP;Berger MF;Wang L;Cimera R;Wang J;Klimstra DS;Saltz L;Ladanyi M;Zehir A;Hechtman JF
本文对染色体20 q扩增大肠癌的分子生物学和临床特征进行了综合分析。来自患有晚期CRC的患者的肿瘤和正常DNA通过MSK-IMPACT进行下一代测序（NGS），并且病例样品的子集进行高分辨率微阵列（Oncoscan）。用癌症基因组图谱（TCGA）CRC数据评估基因组拷贝数和转录本表达之间的关系。在用MSK-IMPACT测序的CRC患者（n=401）中，148例（37%）有20 q增益，30例（7%）有20 q扩增。在MSK-IMPACT和TCGA数据集中，BCL 2L 1是最常扩增的20 q癌基因。然而，SRC是唯一被识别的20 q癌基因，mRNA上调与RAS/RAF突变之间存在显著的负相关关系（OR：-0.4 +/-0.2，p=0.02）。与20 q二倍体CRC相比，20 q增益/扩增与野生型（WT）KRAS（p<0.001）和BRAF（p=0.01）、微卫星稳定性（MSS）（p<0.001）、远端原发性肿瘤（p<0.001）和突变型TP 53（p<0.001）相关，但与分期无关。在多变量分析中，与二倍体20 q相比，观察到染色体20 q增益（p=0.02）或扩增（p=0.04）的转移日期的总生存期更长。
Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC 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 to 20q diploid CRC, 20q gain/amplification was associated with wild-type (WT) KRAS (p<0.001) and BRAF (p=0.01), microsatellite stability (MSS) (p<0.001), distal primary tumors (p<0.001), and mutant TP53 (p<0.001), but not stage. On multi-variate analysis, longer overall survival from date of metastasis was observed with chromosome 20q gain (p=0.02) or amplification (p=0.04) compared to diploid 20q.