Landscape of homologous recombination deficiencies in solid tumours: analyses of two independent genomic datasets.
BMC Cancer
; 22(1): 13, 2022 Jan 03.
Article
in En
| MEDLINE
| ID: mdl-34979999
ABSTRACT
BACKGROUND:
DNA repair deficiencies are characteristic of cancer and homologous recombination deficiency (HRD) is the most common. HRD sensitizes tumour cells to PARP inhibitors so it is important to understand the landscape of HRD across different solid tumour types.METHODS:
Germline and somatic BRCA mutations in breast and ovarian cancers were evaluated using sequencing data from The Cancer Genome Atlas (TCGA) database. Secondly, a larger independent genomic dataset was analysed to validate the TCGA results and determine the frequency of germline and somatic mutations across 15 different candidate homologous recombination repair (HRR) genes, and their relationship with the genetic events of bi-allelic loss, loss of heterozygosity (LOH) and tumour mutation burden (TMB).RESULTS:
Approximately one-third of breast and ovarian cancer BRCA mutations were somatic. These showed a similar degree of bi-allelic loss and clinical outcomes to germline mutations, identifying potentially 50% more patients that may benefit from precision treatments. HRR mutations were present in sizable proportions in all tumour types analysed and were associated with high TMB and LOH scores. We also identified numerous BRCA reversion mutations across all tumour types.CONCLUSIONS:
Our results will facilitate future research into the efficacy of precision oncology treatments, including PARP and immune checkpoint inhibitors.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Breast Neoplasms
/
BRCA1 Protein
/
BRCA2 Protein
/
Homologous Recombination
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
BMC Cancer
Journal subject:
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM