Dataset Information

Simultaneous detection of genetic and copy number alterations in BRCA1/2 genes.

ABSTRACT: Germline mutations in BRCA1 and BRCA2 genes (BRCA1/2) predispose to hereditary breast and ovarian cancer syndrome (HBOC), and their dysregulation increases the risk of cancers. The detection of pathogenic BRCA1/2 variants is essential for the diagnosis and prevention of HBOC, and for offering treatment decisions for patients. Therefore, there is a growing demand for the development of accurate, rapid assay systems that simultaneously detect pathogenic variants and copy number alterations. Here, we tested Thermo Fisher Scientific's newly developed Oncomine®BRCA1/2 Panel. We showed that all mutations in standard reference DNA were detected with high accuracy, and that values of allelic fractions were detected with high concordance (R2 = 0.9986). The Oncomine®BRCA1/2 Panel detected 21 pathogenic germline variants in 147 patients with breast and/or ovarian cancer, of which 20 were detected by the previously-launched Ion AmpliSeq™ BRCA1/2 Panel, except for one frameshift mutation. The Oncomine®BRCA1/2 Panel precisely captured one additional frameshift mutation, which is difficult to detect because of the homopolymer site. Large genomic deletion was identified in one sample, which was previously detected by multiplex ligation-dependent probe amplification. Oncomine®BRCA1/2 Panel could accurately detect pathogenic variant and copy number alteration, and be an alternative assay to investigate BRCA1/2 germline and somatic mutations.

SUBMITTER: Hirotsu Y

PROVIDER: S-EPMC5777706 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Simultaneous detection of genetic and copy number alterations in BRCA1/2 genes.

Hirotsu Yosuke Y Ooka Yoshihiko Y Sakamoto Ikuko I Nakagomi Hiroshi H Omata Masao M

Oncotarget 20171206 70

Germline mutations in BRCA1 and BRCA2 genes (BRCA1/2) predispose to hereditary breast and ovarian cancer syndrome (HBOC), and their dysregulation increases the risk of cancers. The detection of pathogenic BRCA1/2 variants is essential for the diagnosis and prevention of HBOC, and for offering treatment decisions for patients. Therefore, there is a growing demand for the development of accurate, rapid assay systems that simultaneously detect pathogenic variants and cop ...[more]

PMID: 29383094

Similar Datasets

Project description:In different species, embryonic aneuploidies and genome-wide errors are a major cause of developmental failure. The increasing number of equine embryos being produced worldwide provides the opportunity to characterize and rank or select embryos based on their genetic profile prior to transfer. Here, we explored the possibility of generic, genome-wide preimplantation genetic testing concurrently for aneuploidies (PGT-A) and monogenic (PGT-M) traits and diseases in the horse, meanwhile assessing the incidence and spectrum of chromosomal and genome-wide errors in in vitro-produced equine embryos. To this end, over 70,000 single nucleotide polymorphism (SNP) positions were genotyped in 14 trophectoderm biopsies and corresponding biopsied blastocysts, and in 26 individual blastomeres from six arrested cleavage-stage embryos. Subsequently, concurrent genome-wide copy number detection and haplotyping by haplarithmisis was performed and the presence of aneuploidies and genome-wide errors and the inherited parental haplotypes for four common disease-associated genes with high carrier frequency in different horse breeds (GBE1, PLOD1, B3GALNT2, MUTYH), and for one color coat-associated gene (STX17) were compared in biopsy-blastocyst combinations. The euploid (n = 12) or fully aneuploid (n = 2) state and the inherited parental haplotypes for 42/45 loci of interest of the biopsied blastocysts were predicted by the biopsy samples in all successfully analyzed biopsy-blastocyst combinations (n = 9). Two biopsies showed a loss of maternal chromosome 28 and 31, respectively, which were confirmed in the corresponding blastocysts. In one of those biopsies, additional complex aneuploidies not present in the blastocyst were found. Five out of six arrested embryos contained chromosomal and/or genome-wide errors in most of their blastomeres, demonstrating their contribution to equine embryonic arrest in vitro. The application of the described PGT strategy would allow to select equine embryos devoid of genetic errors and pathogenetic variants, and with the variants of interest, which will improve foaling rate and horse quality. We believe this approach will be a gamechanger in horse breeding.

Dataset Information

Simultaneous detection of genetic and copy number alterations in BRCA1/2 genes.

Publications

Simultaneous detection of genetic and copy number alterations in <i>BRCA1/2</i> genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets