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Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer

ABKEVICH, V ; TIMMS, K. M ; TRAN, T. V ; WILLIAMS, D ; ILIEV, D ; JAMMULAPATI, S ; FITZGERALD, L. M ; KRIVAK, T ; DELOIA, J. A ; GUTIN, A ; MILLS, G. B ; LANCHBURY, J. S ; HENNESSY, B. T ; POTTER, J ; CAREY, M. S ; MEYER, L. A ; SMITH-MCCUNE, K ; BROADDUS, R ; LU, K. H ; CHEN, J

British journal of cancer, 2012-11, Vol.107 (10), p.1776-1782 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Título:
Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
Autor: ABKEVICH, V ; TIMMS, K. M ; TRAN, T. V ; WILLIAMS, D ; ILIEV, D ; JAMMULAPATI, S ; FITZGERALD, L. M ; KRIVAK, T ; DELOIA, J. A ; GUTIN, A ; MILLS, G. B ; LANCHBURY, J. S ; HENNESSY, B. T ; POTTER, J ; CAREY, M. S ; MEYER, L. A ; SMITH-MCCUNE, K ; BROADDUS, R ; LU, K. H ; CHEN, J
Assuntos: Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; BRCA1 Protein - genetics ; BRCA2 Protein - genetics ; Carcinoma, Ovarian Epithelial ; Cell Line, Tumor ; Cohort Studies ; Disease-Free Survival ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins - genetics ; Female ; Female genital diseases ; Genetics & Genomics ; Gynecology. Andrology. Obstetrics ; Humans ; Loss of Heterozygosity ; Medical sciences ; Middle Aged ; Neoplasms, Glandular and Epithelial - genetics ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Recombinational DNA Repair ; Tumors
É parte de: British journal of cancer, 2012-11, Vol.107 (10), p.1776-1782
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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These authors contributed equally to this work.
Descrição: Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH). Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10(-11)). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10(-5) and 10(-29)), and identified breast and pancreatic cell lines with BRCA defects. The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer

ABKEVICH, V ; TIMMS, K. M ; TRAN, T. V ; WILLIAMS, D ; ILIEV, D ; JAMMULAPATI, S ; FITZGERALD, L. M ; KRIVAK, T ; DELOIA, J. A ; GUTIN, A ; MILLS, G. B ; LANCHBURY, J. S ; HENNESSY, B. T ; POTTER, J ; CAREY, M. S ; MEYER, L. A ; SMITH-MCCUNE, K ; BROADDUS, R ; LU, K. H ; CHEN, J

Basingstoke: Nature Publishing Group

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