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Deletion of Chromosome 4q Predicts Outcome in Stage II Colon Cancer Patients

机译:删除4q染色体可预测II期结肠癌患者的结果

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Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters to identify high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, have been established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not yet been investigated for this specific group of patients. The aim of the present study was to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer.Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples were hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction.Results: Stage II colon cancers of patients who had relapse of disease showed significantly more losses on chromosomes 4, 5, 15q, 17q and 18q. In the microsatellite stable (MSS) subgroup (n=28), only loss of chromosome 4q22.1–4q35.2 was significantly associated with disease relapse (p < 0.05, FDR < 0.15). No differences in clinicopathological characteristics between patients with and without relapse were observed.Conclusion: In the present series of MSS stage II colon cancer patients losses on 4q22.1–4q35.2 were associated with worse outcome and these genomic alterations may aid in selecting patients for adjuvant therapy.
机译:背景:所有II期结肠癌患者中约有30%会复发并死于疾病。目前,尚无确定可从辅助化疗中受益的高危II期结肠癌患者的客观参数。根据传统的组织病理学特征,对高危II期结肠癌患者的定义是不准确的。因此,需要更客观和鲁棒的标记来预测复发。 DNA拷贝数畸变已被证明是可靠的预后标志物,但尚未针对这一特定患者群体进行过研究。本研究的目的是确定可预测II期结肠癌患者肿瘤复发的染色体畸变。材料与方法:从40份甲醛固定的石蜡包埋的II期结肠癌样本中分离DNA,并具有广泛的临床病理数据。使用比较基因组杂交(CGH)阵列杂交样品,以确定DNA拷贝数变化,并通过PCR确定微卫星稳定性。为了分析患有和未患有肿瘤复发的II期结肠癌患者之间的差异,我们进行了Wilcoxon秩和检验并进行了多次测试校正。结果:患有疾病复发的II期结肠癌患者在第4、5号染色体上的损失明显更多,15q,17q和18q。在微卫星稳定(MSS)亚组(n = 28)中,仅染色体4q22.1–4q35.2的丢失与疾病复发显着相关(p <0.05,FDR <0.15)。结论:在本系列MSS II期结肠癌患者中,4q22.1–4q35.2的患者丢失与预后较差有关,这些基因组改变可能有助于选择患者用于辅助治疗。

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