全面肿瘤分析揭示了腹膜转移与原发性结直肠腺癌之间独特的分子差异。
Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.
机构信息
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
出版信息
J Surg Oncol. 2020 Jun;121(8):1320-1328. doi: 10.1002/jso.25899. Epub 2020 Mar 12.
BACKGROUND AND OBJECTIVES
Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined.
METHODS
We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test-defined as pathogenic (PATH).
RESULTS
Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right-sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left-sided PM. Nine percent of pCRC and 6% of PM were MSI-high (P = NS). There was no difference in TMB-high, TMB-intermediate, or TMB-low between PM and pCRC.
CONCLUSIONS
PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.
背景与目的
原发性结直肠癌（pCRC）的腹膜转移（PM）预后较差，但分子差异尚不清楚。
方法
我们比较了 Caris Life Sciences 中未配对的 pCRC 和 PM 患者的肿瘤样本。检测包括 592 个基因的下一代测序、微卫星不稳定性（MSI）和肿瘤突变负荷（TMB）。突变被定义为致病性（PATH）。
结果
617 例 pCRC 和 348 例 PM 患者的性别（55%为男性）和年龄（中位数 59 岁）相似。PM 和 pCRC 中的 KRAS、BRAF、SMAD2、SMAD4 和 PTEN 中存在相似的 PATH。与 PM 相比，pCRC 中的 APC（76%比 48%，P<0.01）、ARID1A（29%比 12%，P<0.05）、TP53（72%比 53%，P<0.01）、PIK3CA（22%比 15%，P<0.05）和 FBXW7（13%比 7%，P<0.01）的 PATH 增加。黏液性 PM 中 GNAS 的 PATH 更多（19%比 8%，P=0.032），而非黏液性 PM 中 BRAF 的 PATH 更多（13%比 8%，P=0.027）。右侧 PM 中 APC（39%比 68%，P<0.0001）、ARID1A（7%比 38%，P<0.004）和 TP53（48%比 65%，P=0.033）的 PATH 减少，但左侧 PM 无差异。9%的 pCRC 和 6%的 PM 为 MSI 高（P=NS）。PM 和 pCRC 之间 TMB 高、TMB 中、TMB 低无差异。
结论
PM 中 KRAS 突变率与 pCRC 相似，GNAS（黏液性）和 BRAF（非黏液性）的 PATH 增加。PM 和 pCRC 肿瘤之间未发现 MSI 或 TMB 差异。这些发现为 PM 的分子谱研究提供了信息。
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