Comprehensive Analyses of Somatic Copy Number Alterations and Mutations Based on the Adenoma–Carcinoma Sequence

IF 3.1 2区医学 Q2 GENETICS & HEREDITY

Genes, Chromosomes & Cancer Pub Date : 2024-09-11 DOI:10.1002/gcc.23267

Tamotsu Sugai, Mitsumasa Osakabe, Noriyuki Uesugi, Wataru Habano, Naoki Yanagawa, Hiromu Suzuki

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Abstract

Aims

Identifying molecular alterations in the adenoma and carcinoma components within the same tumor would greatly contribute to understanding the neoplastic progression of early colorectal cancer.

Methods and Results

We examined somatic copy number alterations (SCNAs) and mutations involved in the adenoma and carcinoma components obtained from the same tumor in 46 cases of microsatellite-stable carcinoma in adenoma, using a genome-wide SNP array and gene mutation panel. In addition, we also performed hierarchical clustering to determine the SCNA frequencies in the tumors, resulting in stratification of the samples into two subgroups according to SCNA frequency. Subgroup 1 was characterized by multiple SCNAs and carcinoma components exclusively, while Subgroup 2 was characterized by a low frequency of SCNAs and both the adenoma and carcinoma components. The numbers of total genes and genes with gains were higher in the carcinoma than adenoma components. The three most frequent gains in both components were located at 1p36.33–1q44, 2p25.3–2q37.3, and 3p26.3–3q29. However, no candidate genes mapped to these regions. APC and KRAS mutations were common in both components, whereas the frequency of TP53 mutations was statistically higher in the carcinoma than adenoma component. However, TP53 mutations were not correlated with SCNA frequency.

Conclusions

We suggest that considerable SCNAs and TP53 mutations are required for progression from adenoma to carcinoma within the same intramucosal neoplastic lesion.

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基于腺瘤-癌序列的体细胞拷贝数畸变和突变综合分析

目的识别同一肿瘤中腺瘤和癌成分的分子改变将大大有助于了解早期结直肠癌的肿瘤进展。方法和结果我们利用全基因组 SNP 阵列和基因突变面板，对 46 例微卫星稳定的腺瘤癌病例进行了体细胞拷贝数改变（SCNA）和基因突变的检测。此外，我们还进行了分层聚类，以确定肿瘤中的 SCNA 频率，从而根据 SCNA 频率将样本分为两个亚组。亚组 1 的特点是有多个 SCNA，而且只有癌成分；亚组 2 的特点是 SCNA 频率低，而且既有腺瘤成分也有癌成分。癌成分中的总基因数和增益基因数均高于腺瘤成分。这两种成分中最常见的三个增益基因分别位于 1p36.33-1q44、2p25.3-2q37.3 和 3p26.3-3q29。但是，没有候选基因映射到这些区域。APC和KRAS突变在这两种成分中都很常见，而TP53突变的频率在统计学上在癌成分中高于腺瘤成分。然而，TP53 突变与 SCNA 频率无关。结论我们认为，在同一粘膜内肿瘤病变中，从腺瘤发展为癌需要相当多的 SCNA 和 TP53 突变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes, Chromosomes & Cancer 医学-遗传学

CiteScore

7.00

自引率

8.10%

发文量

审稿时长

4-8 weeks

期刊介绍： Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.