Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition? | UAMS Department of Biomedical Informatics

Leukemia. 2018 Jul;32(7):1561-1566. doi: 10.1038/s41375-018-0017-0. Epub 2018 Feb 2

Pawlyn C, Loehr A, Ashby C, Tytarenko R, Deshpande S, Sun J, Fedorchak K, Mughal T, Davies FE, Walker BA, Morgan GJ

Abstract

PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be detected in patient samples, supporting a potential role for PARP inhibition in MM. Using results from targeted next-generation sequencing studies (FoundationOne^® Heme), we analyzed HRD-LOH in patients at all disease stages (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71), treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to identify HRD-LOH segments. We demonstrated HRD-LOH in MM samples, increasing as…