Fig. 4: Gene fusions and isoform switching detected by RNA sequencing.

a Clinical characteristics of patients in which IGH-@, IGL-@, and MALAT1 fusions were identified. Tumors are displayed in chronological order by patient, with the primary tumor at the top and latest recurrence at the bottom. “1 fusion” refers to a translocation with one other gene. LOH BRCA1/2 allele-specific loss of heterozygosity; PARPi PARP inhibitor. b Example of MALAT1-IGH-@ gene fusion IGV tracks from patient 9. Junction reads (red, middle track) represent split RNA-seq reads used to map the fusion breakpoint. Spanning reads (black, bottom track) represent paired-end reads of fragments that span, but do not directly overlap, the fusion breakpoint. c Expression of total BRCA2 (all isoforms) in recurrences vs. normal samples (n = 66 biologically independent samples from 39 patients). Data are expressed as mean values +/– SD. NS not significant. Adjusted p-values were computed based on linear modeling of mean-variance trends (limma). d BRCA2 isoform usage (BRCA2 isoform expression normalized to total BRCA2 expression) in recurrences vs. normal samples; q-values computed using DEXSeq within isoformSwitchAnalyzer. e BRCA2 isoforms involved in isoform switching event. NMD nonsense-mediated decay, UTR untranslated region. f BRCA2 isoform expression by sample and group for entire RNA sequencing cohort. g Overall survival (OS) curve for patients that expressed BRCA2-001/Short in any (primary or recurrent) breast tumor compared to those that did not. Survival proportions and p-value were calculated using a Cox proportional hazards model tested for significant associations with ER status, age at diagnosis, tumor stage at diagnosis, and patient recurrent status (α = 0.05, see Methods).