Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas.

Luuk Harbers,Marcin Nicos,Magda Bienko,Dimitri Poddighe,Nicola Crosetto,Federico Agostini

doi:10.3389/fonc.2021.700568

Abstract

Somatic copy number alterations (SCNAs) are a pervasive trait of human cancers that contributes to tumorigenesis by affecting the dosage of multiple genes at the same time. In the past decade, The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) initiatives have generated and made publicly available SCNA genomic profiles from thousands of tumor samples across multiple cancer types. Here, we present a comprehensive analysis of 853,218 SCNAs across 10,729 tumor samples belonging to 32 cancer types using TCGA data. We then discuss current models for how SCNAs likely arise during carcinogenesis and how genomic SCNA profiles can inform clinical practice. Lastly, we highlight open questions in the field of cancer-associated SCNAs.

Highlights

A Bit of SemanticsCancer cells almost invariably harbor altered karyotypes
SCNAs defined as amplifications or deletions longer than 10 kb and spanning at most 75% of the corresponding chromosome arm represent the main type of alteration in 28 out of 32 (87.5%) tumor types for which copy number data are available in The Cancer Genome Atlas (TCGA) (Figure 1A)
Indels represent the second most frequent type of alteration in these tumors, while they prevail over SCNAs in thyroid carcinomas (THCA), thymomas (THYM), kidney renal clear cell carcinomas (KIRC), and pheochromocytomas and paragangliomas (PCPG)

Summary

Introduction

Deviations from the normal karyotype can range from entire or partial gains or losses of chromosomes and large intra-chromosomal inversions or translocations between different chromosomes, to more complex rearrangements, such as “chromothripsis” (where massive genomic rearrangements are generated in a single event and are localized to isolated chromosomal regions) [1]. Any deviation from the 2n copy number state of a region in the genome represents a copy number alteration (CNA). Gains or losses of entire chromosomes have historically been referred to as aneuploidy or whole chromosome aneuploidy, while gains or losses of chromosomal arms or smaller chromosomal regions have been variably termed segmental or partial aneuploidy, (focal) CNAs or small insertions or deletions (indels), depending on the size of the genomic region amplified or deleted [2]. The mechanisms responsible for whole chromosome CNAs, arm-level CNAs, focal

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