CD74

Overview

CD74 (also known as MHC class II invariant chain or HLA-DR antigen-associated invariant chain) encodes a type II transmembrane protein involved in antigen presentation and immune cell signaling. In lung adenocarcinoma, CD74 has been identified as a fusion partner in oncogenic CD74-NRG1 fusions, which activate ErbB2/ErbB3 (HER2/HER3) receptor signaling and represent a rare but potentially actionable driver event in LUAD patients who otherwise lack canonical oncogenic drivers.

Alterations observed in the corpus

  • CD74-NRG1 fusion — identified in 1 patient with advanced recurrent/metastatic LUAD profiled by MSK-IMPACT in a 860-patient precision oncology cohort; classified among rare fusion events alongside FGFR3-TACC3 and SND1-BRAF PMID:28336552

Cancer types (linked)

  • LUAD: CD74-NRG1 fusion is a rare driver event in lung adenocarcinoma; the fusion was identified in the MSK-IMPACT prospective cohort at a frequency of ~0.1% (1/860 patients) among recurrent/metastatic cases PMID:28336552

Co-occurrence and mutual exclusivity

  • The CD74-NRG1 fusion was identified as a single-patient event in the MSK-IMPACT LUAD cohort; its relationship to canonical drivers (EGFR, KRAS, ALK, ROS1) was not specifically described but NRG1 fusions are generally considered mutually exclusive with other oncogenic drivers in LUAD PMID:28336552

Therapeutic relevance

  • NRG1 fusions (including CD74-NRG1) activate HER2/HER3 signaling and may confer sensitivity to HER2/HER3-targeted therapies such as afatinib and pertuzumab, although evidence was not directly reported for this patient in the MSK-IMPACT cohort PMID:28336552

Open questions

  • Matched therapy uptake and clinical benefit for the CD74-NRG1 fusion patient were not reported in the MSK-IMPACT cohort analysis; the optimal therapeutic strategy for NRG1-fusion LUAD remains an area of active investigation PMID:28336552

Sources

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