Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes

Abstract

Copy number aberrations (CNA) are one of the most important classes of genomic mutations related to oncogenetic effects. In the past three decades, a vast amount of CNA data has been generated by molecular-cytogenetic and genome sequencing based methods. While this data has been instrumental in the identification of cancer-related genes and promoted research into the relation between CNA and histo-pathologically defined cancer types, the heterogeneity of source data and derived CNV profiles pose great challenges for data integration and comparative analysis. Furthermore, a majority of existing studies have been focused on the association of CNA to pre-selected “driver” genes with limited application to rare drivers and other genomic elements. In this study, we developed a bioinformatics pipeline to integrate a collection of 44,988 high-quality CNA profiles of high diversity. Using a hybrid model of neural networks and attention algorithm, we generated the CNA signatures of 31 cancer subtypes, depicting the uniqueness of their respective CNA landscapes. Finally, we constructed a multi-label classifier to identify the cancer type and the organ of origin from copy number profiling data. The investigation of the signatures suggested common patterns, not only of physiologically related cancer types but also of clinico-pathologically distant cancer types such as different cancers originating from the neural crest. Further experiments of classification models confirmed the effectiveness of the signatures in distinguishing different cancer types and demonstrated their potential in tumor classification.

Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells

“…CNVs are one of the most important classes of genomic mutations related to carcinogenesis [29]. CNVs involve deletions or amplifications of large contiguous segments of the genome, including tumor-suppressive genes and oncogenic genes, respectively [29]. Amplification of genes is occasionally associated with transcriptional upregulation of the amplified gene [30].…”

GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment

“…Copy number variation (CNV) is a class of structural genomic variation, which is generally considered to be one of the major factors influencing tumorigenesis and progression [38]. CNV is mainly classified as copy number heterozygous amplifications and copy number heterozygous deletions, which can induce aberrant expression of oncogenes, DNA repair genes, and other genes to influence tumor formation [39][40][41][42]. We analyzed the variation of CNV frequency among GPXs family in pan-cancer.…”

Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

“…We began by analyzing over 39,000 patient tumors in the large-scale Progenetix database 62,63 , omitting tumors in the database that were also in The Cancer Genome Atlas (TCGA) cohort 64 , to quantify the relative prevalences of the 10 loss and 7 gain chromosomal events in glioblastoma in comparison to other loss-gain co-aneuploidy events occurring in other types of cancer. In this analysis, we considered p and q arms separately and focused on autosomes because Progenetix does not curate the sex of each subject.…”

“…We downloaded the metadata from tumors from 118,238 patients from the Progenetix 63 database on January 5, 2023 (https://progenetix.org/). The metadata included histological diagnosis identifiers, which are specified using a hierarchical system of National Cancer Institute (NCI) Thesaurus Terms.…”