Dataset Information

Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer.

ABSTRACT: The first genomic scar-based homologous recombination deficiency (HRD) measures were produced using SNP arrays. As array-based technology has been largely replaced by next generation sequencing approaches, it has become important to develop algorithms that derive the same type of genomic scar scores from next generation sequencing (whole exome "WXS", whole genome "WGS") data. In order to perform this analysis, we introduce here the scarHRD R package and show that using this method the SNP array-based and next generation sequencing-based derivation of HRD scores show good correlation (Pearson correlation between 0.73 and 0.87 depending on the actual HRD measure) and that the NGS-based HRD scores distinguish similarly well between BRCA mutant and BRCA wild-type cases in a cohort of triple-negative breast cancer patients of the TCGA data set.

SUBMITTER: Sztupinszki Z

PROVIDER: S-EPMC6028448 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer.

Sztupinszki Zsofia Z Diossy Miklos M Krzystanek Marcin M Reiniger Lilla L Csabai István I Favero Francesco F Birkbak Nicolai J NJ Eklund Aron C AC Syed Ali A Szallasi Zoltan Z

NPJ breast cancer 20180702

The first genomic scar-based homologous recombination deficiency (HRD) measures were produced using SNP arrays. As array-based technology has been largely replaced by next generation sequencing approaches, it has become important to develop algorithms that derive the same type of genomic scar scores from next generation sequencing (whole exome "WXS", whole genome "WGS") data. In order to perform this analysis, we introduce here the scarHRD R package and show that using this method the SNP array- ...[more]

PMID: 29978035

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Project description:BackgroundWith the widespread use of next-generation sequencing (NGS) in clinical practice, an increasing number of biomarkers that predict a response to anti-tumor therapy in non-small cell lung cancer (NSCLC) has been identified. However, validated biomarkers that can be used to detect a response to platinum-based chemotherapy remain unavailable. Several studies have suggested that homologous recombination deficiency (HRD) may occur in response to platinum-based chemotherapy in ovarian cancer and breast cancer. However, currently there is a lack of proven and reliable HRD markers that can be used to screen for patients who may benefit from platinum-based chemotherapy, especially in NSCLC.MethodsNGS was used to screen for gene mutations, including homologous recombination (HR) genes and common driver gene mutations in NSCLC. Cox regression analysis was performed to identify potential clinicopathological or gene mutation factors associated with survival in patients receiving platinum-based chemotherapy, while Kaplan-Meier analysis with the log-rank test was performed to assess the effect of HR gene mutations on progression-free survival (PFS).ResultsIn a retrospective cohort of 129 patients with advanced NSCLC, 54 who received platinum-based chemotherapy with or without anti-angiogenic therapy were included in the analysis. Univariate and multivariate Cox proportional hazard regression analyses showed that HR gene mutations were associated with platinum-based chemotherapy sensitivity. Efficacy results indicated that the objective response rates (ORR) for patients with BRCA1/2 mutations and BRCA1/2 wild type were 75% and 30.4% (p=0.041), while the median PFS was 7.5 and 5.5 months (hazard ratio [HR], 0.52; 95% CI, 0.27-1.00; p=0.084), respectively. The ORRs of patients with HR gene mutations and HR gene wild type were 60% and 23.6% (p=0.01), and the median PFS was 7.5 and 5.2 months (HR, 0.56; 95% CI, 0.32-0.97; p=0.033), respectively.ConclusionsHR gene mutations show potential as promising biomarkers that may predict sensitivity to platinum-based chemotherapy in advanced and metastatic NSCLC.

Dataset Information

Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer.

Publications

Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer.

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