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IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma.

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.

SUBMITTER: Zhu S

PROVIDER: S-EPMC5931118 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma.

Zhu Sha S Ward B Marie BM Yu Jun J Matthew-Onabanjo Asia N AN Janusis Jenny J Hsieh Chung-Cheng CC Tomaszewicz Keith K Hutchinson Lloyd L Zhu Lihua Julie LJ Kandil Dina D Shaw Leslie M LM

JCI insight 20180419 8

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 chan ...[more]

PMID: 29669935

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High Frequency of ERBB2 Activating Mutations in Invasive Lobular Breast Carcinoma with Pleomorphic Features.

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