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黏液性结直肠癌中拷贝数畸变率降低。

Reduced rate of copy number aberrations in mucinous colorectal carcinoma.

作者信息

Hugen Niek, Simmer Femke, Mekenkamp Leonie J M, Koopman Miriam, van den Broek Evert, de Wilt Johannes H W, Punt Cornelis J A, Ylstra Bauke, Meijer Gerrit A, Nagtegaal Iris D

机构信息

Department of Surgery, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.

Department of Pathology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.

出版信息

Oncotarget. 2015 Sep 22;6(28):25715-25. doi: 10.18632/oncotarget.4706.

Abstract

BACKGROUND

Mucinous carcinoma (MC) is found in 10%-15% of colorectal cancer (CRC) patients. It differs from the common adenocarcinoma (AC) in histopathological appearance and clinical behavior.

METHODS

Genome-wide DNA copy number and survival data from MC and AC primary CRC samples from patients from two phase III trials (CAIRO and CAIRO2) was compared. Chromosomal copy number data from The Cancer Genome Atlas (TCGA) was used for validation. Altogether, 470 ACs were compared to 57 MCs.

RESULTS

MC showed a reduced amount of copy number aberrations (CNAs) compared with AC for the CAIRO/CAIRO2 cohort, with a median amount of CNAs that was 1.5-fold lower (P = 0.002). Data from TCGA also showed a reduced amount of CNAs for MC. MC samples in both cohorts displayed less gain at chromosome 20q and less loss of chromosome 18p. A high rate of chromosomal instability was a strong negative prognostic marker for survival in MC patients from the CAIRO cohorts (hazard ratio 15.60, 95% CI 3.24-75.05).

CONCLUSIONS

Results from this study indicate that the distinct MC phenotype is accompanied by a different genetic basis when compared with AC and show a strong association between the rate of chromosomal instability and survival in MC patients.

摘要

背景

黏液腺癌(MC)见于10%-15%的结直肠癌(CRC)患者中。它在组织病理学表现和临床行为上与常见的腺癌(AC)不同。

方法

比较了来自两项III期试验(CAIRO和CAIRO2)患者的MC和AC原发性CRC样本的全基因组DNA拷贝数和生存数据。来自癌症基因组图谱(TCGA)的染色体拷贝数数据用于验证。总共将470例AC与57例MC进行了比较。

结果

对于CAIRO/CAIRO2队列,MC与AC相比显示出较少的拷贝数畸变(CNA),CNA的中位数低1.5倍(P = 0.002)。TCGA的数据也显示MC的CNA较少。两个队列中的MC样本在染色体20q上显示较少的增益,在染色体18p上显示较少的缺失。高频率的染色体不稳定是CAIRO队列中MC患者生存的强烈负面预后标志物(风险比15.60,95%CI 3.24-75.05)。

结论

本研究结果表明,与AC相比,独特的MC表型伴有不同的遗传基础,并显示染色体不稳定率与MC患者生存之间存在强烈关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96ed/4694861/a4fa331df0f8/oncotarget-06-25715-g001.jpg

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