Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer - PubMed (original) (raw)

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

Zsofia Sztupinszki et al. NPJ Breast Cancer. 2018.

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.

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Conflict of interest statement

N.J.B., A.C.E., and Zo.S are listed as co-inventors on a patent on telomeric allelic imbalance, which is owned by Children’s Hospital Boston and licensed to Myriad Genetics. The remaining authors declare no competing interests.

Figures

Fig. 1

Fig. 1

Correlation between Affymetrix SNP 6.0 array-based and whole exome sequencing-based measurements of homologous recombination deficiency (telomeric allelic imbalance, loss of heterozygosity, large-scale transitions, and the sum of these estimates)

Fig. 2

Fig. 2

Distribution of HRD-sum values in BRCA1/2 deficient and in BRCA1/2 intact triple-negative breast cancer samples from TCGA. HRD-sum values were determined with the scarHRD R package

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