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Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3^VNTR polymorphisms and gene co-expression.

ABSTRACT: Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3^VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97-1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10^-12) but not in the rest of breast cancer subtypes.

SUBMITTER: Fores-Martos J

PROVIDER: S-EPMC8433453 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3<sup>VNTR</sup> polymorphisms and gene co-expression.

Fores-Martos Jaume J Cervera-Vidal Raimundo R Sierra-Roca Julia J Lozano-Asencio Carlos C Fedele Vita V Cornelissen Sten S Edvarsen Hege H Tadeo-Cervera Irene I Eroles Pilar P Lluch Ana A Tabares-Seisdedos Rafa R Falcó Antonio A Van't Veer Laura J LJ Schmidt Marjanka M Quigley David A DA Børresen-Dale Anne-Lise AL Kristensen Vessela N VN Balmain Allan A Climent Joan J

NPJ breast cancer 20210910 1

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3<sup>VNRT</sup> polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend toward ...[more]

PMID: 34508103

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Project description:ObjectivesIn breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations.MethodsForty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated.ResultsThe overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations.ConclusionsData obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Dataset Information

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3^VNTR polymorphisms and gene co-expression.

Publications

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3<sup>VNTR</sup> polymorphisms and gene co-expression.

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Dataset Information

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression.

Publications

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3<sup>VNTR</sup> polymorphisms and gene co-expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3^VNTR polymorphisms and gene co-expression.