UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; Department of Surgery; Department of Pathology; UMass Metabolic Network

Publication Date


Document Type



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

Rights and Permissions

Copyright © 2018, American Society for Clinical Investigation. Publisher pdf posted as allowed by the publisher's open access policy at

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

Journal/Book/Conference Title

JCI insight

Related Resources

Link to Article in PubMed

PubMed ID




To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.