BAC CGH array profiling using Phi29-amplified colon mucosa of microdissected samples from APC and MYH mutation carriers.. Homo sapiens

Details of the series are available in the publication Cardoso J. et al., “Chromosomal instability in MYH- and APC-mutant adenomatous polyps”, Cancer Research, accepted for publication. Abstract of the publication: “The vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.” Keywords: repeat, BAC, CGH Overall design: Details of the series are available in the publication Cardoso J. et al., "Chromosomal instability in MYH- and APC-mutant adenomatous polyps", Cancer Research 2006 Mar 1;66(5):2514-9.

本系列数据集的详细信息可参阅论文Cardoso J.等人发表于《Cancer Research》（已接收待刊）的《Chromosomal instability in MYH- and APC-mutant adenomatous polyps》（MYH与APC突变型腺瘤性息肉的染色体不稳定性）。该论文摘要如下："绝大多数结直肠癌均存在遗传不稳定性，可分为染色体不稳定性（chromosomal instability, CIN）与微卫星不稳定性（microsatellite instability, MIN）两种类型。根据定义，染色体不稳定性肿瘤均为非整倍体；而由错配修复功能缺失引发的微卫星不稳定型结直肠癌通常为近二倍体。近期研究发现，MYH基因的双等位基因生殖系突变可导致MAP（MYH相关息肉病，MYH associated polyposis）——一种以多发结直肠息肉为特征的常染色体隐性遗传易感综合征，该病症常与由种系APC突变引发的显性遗传性家族性腺瘤性息肉病（familial adenomatous polyposis, FAP）难以区分。本研究通过联合激光捕获显微切割（laser-capture microdissection）、等温基因组DNA扩增（isothermal genomic DNA amplification）以及阵列比较基因组杂交（array-CGH，comparative genomic hybridization）技术，对MYH突变型与APC突变型息肉进行了分析。我们将平滑分位数回归（smoothed quantile regression）方法应用于MAP与FAP的基因组图谱，以甄别主要发生拷贝数扩增或缺失的染色体。高达80%的MAP息肉存在非整倍体改变，这一比例显著高于FAP息肉中的60%。MAP与FAP腺瘤均具有频繁出现染色体1p、17、19及22缺失，以及染色体7、13拷贝数扩增的特征。在MYH驱动的肿瘤发生早期即可检测到非整倍体，这一发现提示染色体不稳定性可能在MAP患者中显著促进肿瘤进展加速、癌症风险升高以及不良预后。"关键词：重复序列，细菌人工染色体（BAC），比较基因组杂交（CGH）实验整体设计：本系列数据集的详细信息可参阅论文Cardoso J.等人发表于《Cancer Research》2006年3月1日；66(5):2514-9的《Chromosomal instability in MYH- and APC-mutant adenomatous polyps》（MYH与APC突变型腺瘤性息肉的染色体不稳定性）。