Genomics

Dataset Information

0

Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis


ABSTRACT: Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 mutations. We performed whole-genome sequence (WGS) analysis of tumors from 22 TP53 mutation carriers. We observed somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identified near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurred earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, revealed that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising very early in life or in utero.years prior to tumor diagnosis.

PROVIDER: EGAS00001005982 | EGA |

REPOSITORIES: EGA

Similar Datasets

2008-07-16 | E-GEOD-8798 | biostudies-arrayexpress
2020-07-24 | GSE143741 | GEO
| EGAD00001009280 | EGA
2008-07-16 | GSE8798 | GEO
2010-10-21 | E-GEOD-23994 | biostudies-arrayexpress
2021-12-02 | GSE188739 | GEO
2010-10-21 | GSE23994 | GEO
2015-04-10 | E-GEOD-58123 | biostudies-arrayexpress
2012-01-20 | E-GEOD-34258 | biostudies-arrayexpress
| 2349042 | ecrin-mdr-crc