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Next-generation sequencing based detection of BRCA1 and BRCA2 large genomic rearrangements in Chinese cancer patients
Ist Teil von
Frontiers in oncology, 2022-09, Vol.12, p.898916-898916
Ort / Verlag
Frontiers Media S.A
Erscheinungsjahr
2022
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
BRCA1/2
mutation is a biomarker for guiding multiple solid tumor treatment. However, the prevalence of
BRCA1/2
large genomic rearrangements (LGRs) in Chinese cancer patients has not been well revealed partially due to technical difficulties in LGR detection. This study utilized next-generation sequencing (NGS) to analyze the
BRCA1/2
mutation profile, including LGR, in 56126 Chinese cancer patients. We also reported that two ovarian and breast cancer patients with NGS-determined
BRCA1/2
LGR benefited from PARP inhibitors (PARPi). DNA sequencing identified
BRCA1/2
variants (including LGR, pathogenic and likely-pathogenic variants) in 2108 individuals. Seventy patients were discovered to harbor germline LGRs in
BRCA1
and 14 had germline LGRs in
BRCA2
. Among the LGRs detected, exon 1-2 deletion was the predominant LGR (14/70) in
BRCA1
, and exon 22-24 deletion was the most frequent LGR (3/14) in
BRCA2
. Notably, the
BRCA1
exon 7 deletion was a novel LGR and was identified in six patients, suggesting a specific LGR in Chinese cancer patients. The prevalence analysis of
BRCA1
and
BRCA2
LGRs across multiple cancers revealed that
BRCA1
LGR more frequently occurred in ovarian cancer (1.31%, 33/2526), and
BRCA2
LGR was more commonly seen in cholangiocarcinoma (0.47%, 2/425). Two ovarian and breast cancer patients with
BRCA1/2
LGR benefited from PARPi therapy. This is the first study to reveal the
BRCA1/2
LGR profile of a Chinese pan-cancer cohort by using an NGS-based assay. Two breast and ovarian cancer patients harboring NGS-determined
BRCA1/2
LGR benefited from PARPi, indicating that NGS-based detection of
BRCA1/2
LGR has the potential to guide PARPi treatment.