Twenty Years of BRCA1 and BRCA2 Molecular Analysis at MMCI – Current Developments for the Classification of Variants

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F19%3A00078228" target="_blank" >RIV/00209805:_____/19:00078228 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/19:00072208

Result on the web

<a href="https://www.linkos.cz/files/klinicka-onkologie/459/5582.pdf" target="_blank" >https://www.linkos.cz/files/klinicka-onkologie/459/5582.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.14735/amko2019S51" target="_blank" >10.14735/amko2019S51</a>

Result language

angličtina

Original language name

Twenty Years of BRCA1 and BRCA2 Molecular Analysis at MMCI – Current Developments for the Classification of Variants

Original language description

Background: Deleterious mutations in the BRCA1 and BRCA2 genes account for a considerable proportion of dominantly inherited breast and ovarian cancer susceptibility. The laboratory interpretation has always been dependent on the information available at the time of the report conclusion. The aim of this study has been to review the results from the BRCA testing at Masaryk Memorial Cancer Institute (MMCI). Patients and methods: Patients with suspected hereditary predisposition to breast/ovarian cancer, belonging to 7,400 families, were referred by genetic counsellors for BRCA1 and BRCA2 mutation testing at the MMCI from 1999 to the beginning of 2018. Various methods have been used over 20 years of laboratory practice - starting with the Protein Truncation Test and Heteroduplex Analysis via the High Resolution Melting analysis and Sanger sequencing up to Next Generation Sequencing. Results: BRCA1 and BRCA2 mutation screening resulted in the identification of 1,021 families with a germline high-risk BRCA1 mutation and 497 families carrying a high-risk BRCA2 mutation, representing a mutation detection rate of 20.5%. A broad spectrum of unique mutations classified as pathogenic or likely pathogenic has been detected in both genes - 124 in the BRCA1 and 123 in the BRCA2 gene. Other sequence variants (96 unique variants in the BRCA1 and 126 in the BRCA2 gene) have been revised and classified as benign or likely benign. The other 82 unique variants remain classified as of uncertain significance mainly due to a lack of information for inclusion in other groups. All the results are summarised in the tables, including the reasons for their classification. Conclusion: The clinical classification of rare sequence variants identified in the high-risk breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling. Here we present an overview of BRCA mutation frequencies in our region and the retrospective evaluation and eventually reclassification of previously reported rare variants in light of recent findings.

Czech name

—

Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NV15-27695A" target="_blank" >NV15-27695A: Characterization of genetic predisposition to ovarian cancer using Next Gene Sequencing analysis</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Klinická onkologie

ISSN

0862-495X

e-ISSN

—

Volume of the periodical

32

Issue of the periodical within the volume

Suppl2

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

21

Pages from-to

"2S51"-"2S71"

UT code for WoS article

—

EID of the result in the Scopus database

2-s2.0-85071280097