학술논문
Homologous recombination deficiency signatures in gastrointestinal and thoracic cancers correlate with platinum therapy duration
Document Type
article
Author
Erica S. Tsang; Veronika Csizmok; Laura M. Williamson; Erin Pleasance; James T. Topham; Joanna M. Karasinska; Emma Titmuss; Intan Schrader; Stephen Yip; Basile Tessier-Cloutier; Karen Mungall; Tony Ng; Sophie Sun; Howard J. Lim; Jonathan M. Loree; Janessa Laskin; Marco A. Marra; Steven J. M. Jones; David F. Schaeffer; Daniel J. Renouf
Source
npj Precision Oncology, Vol 7, Iss 1, Pp 1-12 (2023)
Subject
Language
English
ISSN
2397-768X
Abstract
Abstract There is emerging evidence about the predictive role of homologous recombination deficiency (HRD), but this is less defined in gastrointestinal (GI) and thoracic malignancies. We reviewed whole genome (WGS) and transcriptomic (RNA-Seq) data from advanced GI and thoracic cancers in the Personalized OncoGenomics trial (NCT02155621) to evaluate HRD scores and single base substitution (SBS)3, which is associated with BRCA1/2 mutations and potentially predictive of defective HRD. HRD scores were calculated by sum of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions scores. Regression analyses examined the association between HRD and time to progression on platinum (TTPp). We included 223 patients with GI (n = 154) or thoracic (n = 69) malignancies. TTPp was associated with SBS3 (p