NRG1 rearrangements are found in multiple solid tumors.

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NRG1 rearrangements are found in multiple solid tumors. NRG1 rearrangements are found in multiple solid tumors. A, A schematic of CD74–NRG1, the most commonly identified genomic rearrangement identified in lung cancers in this series, is shown. The CD74 gene (chromosome 5q) is disrupted and inverted downstream of exon 5 and subsequently ligated to a position upstream of exon 6 of the NRG1 gene. B, Structural features of fusions, involving the indicated 5′ and 3′ chromosomal partners, identified by next-generation DNA sequencing (MSK-IMPACT; n = 17,485 tumors profiled) or targeted RNA-seq (MSK Solid Fusion Assay) are shown. The EGF-like domain is maintained in all fusions identified. C, Fusion junction exons, the associated chromosomal partners, and corresponding transcripts (Ensembl database version 75) are shown for all fusions detected by analyzing the TCGA dataset (n = 8,984 tumors analyzed), with the EGF-like domain indicated, wherever applicable. NRG1 fusion partners are not drawn to scale. The asterisk indicates that two distinct fusions were found in the same tumor sample. D,NRG1 RNA-seq expression is plotted across fusion-positive TCGA cancer types (x-axis) with fusion-positive samples indicated in red. Note that only one NRG1 expression value is plotted for the lung squamous cell carcinoma (LUSC) sample with two distinct fusions. BRCA, breast-invasive carcinoma; HNSC, head and neck squamous cell carcinoma; KIRC, kidney renal clear cell carcinoma; LUAD, lung adenocarcinoma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PRAD, prostate adenocarcinoma; UCS, uterine carcinosarcoma. Alexander Drilon et al. Cancer Discov 2018;8:686-695 ©2018 by American Association for Cancer Research