Dataset Information

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population.

ABSTRACT:

Background

The objective of this study was to determine spectrum and prevalence of germline mutations in TP53 gene among Polish women with early-onset breast cancer (BC), which has not been determined until now.

Methods

A cohort of 100 females with BC diagnosed???30 years of age and with a positive family history of cancer was used as a discovery cohort. 1880 women with BC???45 years old and a control group of 2000 healthy women were genotyped as a replication phase of this study.

Results

Four heterozygous pathogenic missense mutations were detected in a group of 100 patients with early-onset breast cancer. On the basis of software prediction and available literature data, all these variants were defined as pathogenic. None of these TP53 variants were detected among 1880 breast cancer patients and 2000 healthy controls. No large mutations were found among early-onset cases using MLPA reaction.

Conclusion

Germline pathogenic TP53 variants were found in 4% early-onset Polish BC patients. No founder mutations were identified in Polish population. To improve the treatment and surveillance screening, the search for germline TP53 pathogenic variants is recommended for all female BC cases diagnosed???30 years old.

SUBMITTER: Rogoza-Janiszewska E

PROVIDER: S-EPMC7796867 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population.

Rogoża-Janiszewska Emilia E Malińska Karolina K Górski Bohdan B Scott Rodney J RJ Cybulski Cezary C Kluźniak Wojciech W Lener Marcin M Jakubowska Anna A Gronwald Jacek J Huzarski Tomasz T Lubiński Jan J Dębniak Tadeusz T

Breast cancer (Tokyo, Japan) 20200904 1

<h4>Background</h4>The objective of this study was to determine spectrum and prevalence of germline mutations in TP53 gene among Polish women with early-onset breast cancer (BC), which has not been determined until now.<h4>Methods</h4>A cohort of 100 females with BC diagnosed ≤ 30 years of age and with a positive family history of cancer was used as a discovery cohort. 1880 women with BC ≤ 45 years old and a control group of 2000 healthy women were genotyped as a replication phase of this study. ...[more]

PMID: 32888145

Similar Datasets

Project description:BackgroundHeterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.MethodsWe searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.ResultsWe identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.ConclusionsAmong Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

Dataset Information

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population.

Background

Methods

Results

Conclusion

Publications

Prevalence of germline TP53 variants among early-onset breast cancer patients from Polish population.

Similar Datasets

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