Department of Molecular, Cell and Cancer Biology; Department of Surgery; Department of Pathology; UMass Metabolic Network
Cancer Biology | Cellular and Molecular Physiology | Genetic Phenomena | Neoplasms | Oncology
Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC.
Breast cancer, Insulin signaling, Oncology
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Copyright © 2018, American Society for Clinical Investigation. Publisher pdf posted as allowed by the publisher's open access policy at https://insight.jci.org/kiosks/terms.
DOI of Published Version
JCI Insight. 2018 Apr 19;3(8). pii: 97398. doi: 10.1172/jci.insight.97398. [Epub ahead of print] Link to article on publisher's site
Zhu, Sha; Ward, B. Marie; Yu, Jun; Matthew-Onabanjo, Asia N.; Janusis, Jenny; Hsieh, Chung-Cheng; Tomaszewicz, Keith; Hutchinson, Lloyd; Zhu, Lihua Julie; Kandil, Dina; and Shaw, Leslie M., "IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma" (2018). Open Access Articles. 3447.