Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer

被引：20

作者：

Ciani, Yari ^{[1
]}

Fedrizzi, Tarcisio ^{[1
]}

Prandi, Davide ^{[1
]}

Lorenzin, Francesca ^{[1
]}

Locallo, Alessio ^{[1
]}

Gasperini, Paola ^{[1
]}

Franceschini, Gian Marco ^{[1
]}

Benelli, Matteo ^{[1
,2
]}

Elemento, Olivier ^{[3
,4
,5
]}

Fava, Luca L. ^{[1
]}

Inga, Alberto ^{[1
]}

Demichelis, Francesca ^{[1
,3
,4
,5
]}

机构：

[1] Univ Trento, Dept Cellular Computat & Integrat Biol, I-38123 Trento, Italy

[2] Hosp Prato, Bioinformat Unit, I-59100 Prato, Italy

[3] Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10021 USA

[4] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al Sa, New York, NY 10021 USA

[5] Weill Cornell Med, Caryl & Israel Englander Inst Precis Med, New York, NY 10021 USA

来源：

CELL SYSTEMS | 2022年 / 13卷 / 02期

基金：

欧洲研究理事会;

关键词：

PROTEIN STABILITY; 26S PROTEASOME; P53; PROTEIN; MUTANT P53; ANEUPLOIDY; INSTABILITY; CELLS; IDENTIFICATION; PROLIFERATION; MUTATIONS;

D O I：

10.1016/j.cels.2021.10.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pan-cancer studies sketched the genomic landscape of the tumor types spectrum. We delineated the purity and ploidy-adjusted allele-specific profiles of 4,950 patients across 27 tumor types from the Cancer Genome Atlas (TCGA). Leveraging allele-specific data, we reclassified as loss of heterozygosity (LOH) 9% and 7% of apparent copy-number wild-type and gain calls, respectively, and overall observed more than 18 million allelic imbalance somatic events at the gene level. Reclassification of copy-number events revealed associations between driver mutations and LOH, pointing out the timings between the occurrence of point mutations and copy-number events. Integrating allele-specific genomics and matched transcriptomics, we observed that allele-specific gene status is relevant in the regulation of TP53 and its targets. Further, we disclosed the role of copy-neutral LOH in the impairment of tumor suppressor genes and in disease progression. Our results highlight the role of LOH in cancer and contribute to the understanding of tumor progression.

引用

页码：183 / +

页数：19

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