Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2, allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00077971" target="_blank" >RIV/00209805:_____/18:00077971 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/18:00068819

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23390" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23390</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/humu.23390" target="_blank" >10.1002/humu.23390</a>

Result language

angličtina

Original language name

Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2, allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11

Original language description

For 21 putative BRCA1 and BRCA2 splice site variants, the concordance between mRNA analysis and predictions by in silico programswas evaluated. Aberrant splicingwas confirmed for 12 alterations. In silico prediction toolswere helpful to determine for which variantscDNAanalysis iswarranted, however, predictions for variants in the Cartegni consensus region but outside the canonical sites, were less reliable. Learning algorithms like Adaboost and Random Forest outperformed the classical tools. Further validations are warranted prior to implementation of these novel tools in clinical settings. Additionally, we report here for the first time activated cryptic donor sites in the large exon 11 of BRCA2 by evaluating the effect at the cDNA level of a novel tandem duplication (5&apos; breakpoint in intron 4; 3&apos; breakpoint in exon 11) and of a variant disrupting the splice donor site of exon 11 (c.6841+1G &gt; C). Additional sites were predicted, but not activated. These sites warrant further research to increase our knowledge on cis and trans acting factors involved in the conservation of correct transcription of this large exon. This may contribute to adequate design of ASOs (antisense oligonucleotides), an emerging therapy to render cancer cells sensitive to PARP inhibitor and platinum therapies.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LO1413" target="_blank" >LO1413: RECAMO2020</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

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

Name of the periodical

Human mutation

ISSN

1059-7794

e-ISSN

—

Volume of the periodical

39

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

515-526

UT code for WoS article

000426727800005

EID of the result in the Scopus database

2-s2.0-85043236315