Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Department of Computer Science, University of Maryland, College Park, USA.
Genome Med. 2021 May 25;13(1):93. doi: 10.1186/s13073-021-00905-y.
Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood.
In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms.
This analysis revealed a complex picture of factors driving tumor karyotype evolution in which some recurrent chromosomal copy number reflect the chromosome arm-wide gene expression levels of the their normal tissue of tumor origin.
We conclude that the cancer type-specific distribution of chromosomal arm gains and losses is potentially "hardwiring" gene expression levels characteristic of the normal tissue of tumor origin, in addition to broadly modulating the expression of tissue-specific tumor driver genes.
许多癌症具有特定于肿瘤起源组织的反复出现的染色体非整倍性。这种特异性的原因尚不完全清楚。
在这项研究中，我们从癌症基因组图谱（TCGA）中观察了不同癌症类型的染色体臂增益和丢失的频率，并将其与来自基因型组织表达（GTEx）数据库中相应正常组织起源的每条染色体臂的平均基因表达进行了比较，此外还比较了组织特异性癌基因和肿瘤抑制基因在不同染色体臂上的分布。
这项分析揭示了驱动肿瘤核型进化的复杂因素，其中一些反复出现的染色体拷贝数反映了其正常组织起源的染色体臂-wide 基因表达水平。
我们的结论是，染色体臂增益和丢失的癌症类型特异性分布可能是“硬连线”的，其特征是肿瘤起源的正常组织的基因表达水平，此外还广泛调节组织特异性肿瘤驱动基因的表达。
