Dataset Information

Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility.

ABSTRACT: Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and other biological processes in chordoma patients from North America and China. We identified variants that were very rare in general population and internal control datasets and showed evidence for pathogenicity in 265 genes in a whole exome sequencing (WES) dataset of 138 chordoma patients of European ancestry and in a whole genome sequencing (WGS) dataset of 80 Chinese patients with skull base chordoma. Rare and likely pathogenic variants were identified in 32 of 138 European ancestry patients (23%), including genes that are part of notochord development, PI3K/AKT/mTOR, Sonic Hedgehog, SWI/SNF complex and mesoderm development pathways. Rare pathogenic variants in COL2A1, EXT1, PDK1, LRP2, TBXT and TSC2, among others, were also observed in Chinese patients. We identified several rare loss-of-function and predicted deleterious missense variants in germline DNA from patients with chordoma, which may influence chordoma predisposition and reflect a complex susceptibility, warranting further investigation in large studies.

SUBMITTER: Yepes S

PROVIDER: S-EPMC8197919 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility.

Yepes Sally S Shah Nirav N NN Bai Jiwei J Koka Hela H Li Chuzhong C Gui Songbai S McMaster Mary Lou ML Xiao Yanzi Y Jones Kristine K Wang Mingyi M Vogt Aurelie A Zhu Bin B Zhu Bin B Hutchinson Amy A Yeager Meredith M Hicks Belynda B Carter Brian B Freedman Neal D ND Beane-Freeman Laura L Chanock Stephen J SJ Zhang Yazhuo Y Parry Dilys M DM Yang Xiaohong R XR Goldstein Alisa M AM

Cancers 20210530 11

<h4>Background</h4>Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and oth ...[more]

PMID: 34070849

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Dataset Information

Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility.

Publications

Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility.

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