Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F03%3A00007600" target="_blank" >RIV/00209805:_____/03:00007600 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2

Popis výsledku v původním jazyce

About 4% of all BRCA1 and BRCA2 alterations reported to the Breast Information Core database are splice site variants. Only a limited number of them have been studied at the RNA level. By BRCA1 and BRCA2 mutation analysis of breast/ovarian cancer families, we identified two novel and eight previously reported potential splice site mutations, never characterized at the cDNA level before. RT-PCR was performed to determine whether these variants disrupted correct splicing. To ensure efficient detection oftranscripts containing premature termination codons, a nonsense-mediated mRNA decay inhibitor was added to the lymphoblastoid cell lines of the patients before RNA extraction. We found that BRCA1 IVS3+3A&gt;C, 4304G&gt;A (in the last codon of exon 12), and IVS19+2delT and BRCA2 IVS6+1G&gt;A, IVS23-2A&gt;G, and IVS24+1G&gt;A lead to aberrant transcripts in lymphocytes. Therefore, they were considered to be true pathogenic mutations, predisposing carriers to cancers of the hereditary breas

Název v anglickém jazyce

Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2

Popis výsledku anglicky

About 4% of all BRCA1 and BRCA2 alterations reported to the Breast Information Core database are splice site variants. Only a limited number of them have been studied at the RNA level. By BRCA1 and BRCA2 mutation analysis of breast/ovarian cancer families, we identified two novel and eight previously reported potential splice site mutations, never characterized at the cDNA level before. RT-PCR was performed to determine whether these variants disrupted correct splicing. To ensure efficient detection oftranscripts containing premature termination codons, a nonsense-mediated mRNA decay inhibitor was added to the lymphoblastoid cell lines of the patients before RNA extraction. We found that BRCA1 IVS3+3A&gt;C, 4304G&gt;A (in the last codon of exon 12), and IVS19+2delT and BRCA2 IVS6+1G&gt;A, IVS23-2A&gt;G, and IVS24+1G&gt;A lead to aberrant transcripts in lymphocytes. Therefore, they were considered to be true pathogenic mutations, predisposing carriers to cancers of the hereditary breas

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/NC6396" target="_blank" >NC6396: Frekvence a typy de novo zárodečných mutací BRCA1/3 genů ve skupině mladých žen s časným sporad.výskytem nádoru prsu/ovaria ve věku do 40 let bez pozitivní rodinné anamnézy.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2003

Kód důvěrnosti údajů

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

Název periodika

Genes, Chromosomes and Cancer

ISSN

1045-2257

e-ISSN

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Svazek periodika

37

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

314-320

Kód UT WoS článku

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EID výsledku v databázi Scopus

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