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IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma
Sha Zhu, … , Dina Kandil, Leslie M. Shaw
Sha Zhu, … , Dina Kandil, Leslie M. Shaw
Published April 19, 2018
Citation Information: JCI Insight. 2018;3(8):e97398. https://doi.org/10.1172/jci.insight.97398.
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Research Article Oncology

IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma

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Abstract

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.

Authors

Sha Zhu, B. Marie Ward, Jun Yu, Asia N. Matthew-Onabanjo, Jenny Janusis, Chung-Cheng Hsieh, Keith Tomaszewicz, Lloyd Hutchinson, Lihua Julie Zhu, Dina Kandil, Leslie M. Shaw

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Figure 1

Molecular profile of pleomorphic invasive lobular carcinoma.

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Molecular profile of pleomorphic invasive lobular carcinoma.
(A and B) R...
(A and B) Representative images of H&E-stained pleomorphic invasive lobular carcinoma (PILC). (C) Representative image of E-cadherin staining in PILC. (D) Total mutation events across the PILC tumors (n = 17). (E) Distribution of copy number variant types (log2 ratio ≥1 or ≤–1) across the PILC tumors. (F) Mean coverage of sequenced PILC tumors and their matched normal controls. (G) Filtered functional somatic alteration events identified in the PILC tumors. (H) Oncoprint heatmaps of recurrently altered genes in PILC. MUtations For Functional Impact on Network Neighbors (MUFFINN) prediction scores are shown on left. Asterisk indicate samples from the same patient. Scale bar: 20 μm.

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