ROBO1

Overview

ROBO1 encodes roundabout guidance receptor 1, a transmembrane receptor for SLIT ligands that mediates axon repulsion during neural development. In pancreatic ductal adenocarcinoma, ROBO1 undergoes focal copy-number losses and point mutations, implicating the SLIT-ROBO axon guidance pathway as a novel cancer pathway. Loss of SLIT-ROBO signaling may activate MET and WNT pathways downstream.

Alterations observed in the corpus

  • Focal copy-number losses and point mutations identified in pancreatic cancer WES of 142 ICGC tumors; additional mutations found in targeted sequencing; loss of ROBO1 may deregulate MET and WNT pathways PMID:23103869
  • Recurrent focal deletion on chromosome 3p12.3-3p12.2 in SCLC WGS of 110 tumours; co-deleted with FHIT at 3p14.3-3p14.2 as part of the 3p loss landscape PMID:26168399
  • ROBO1 locus identified as a novel focal deletion in lung SqCC in the 1,144-tumor NSCLC landscape study (660 lung ADC, 484 lung SqCC); GISTIC2.0 identified recurrent focal loss at the ROBO1 locus specifically in squamous cell carcinoma. PMID:27158780
  • One of the two most strongly down-regulated chr_3p genes after engineered chr_3p deletion in AALE cells (>15-fold at early passage; >13-fold at late passage), and negatively correlated with chr_3p loss in the pan-cancer TCGA transcriptomic model PMID:29622463.

Cancer types (linked)

  • Pancreatic ductal adenocarcinoma (PAAD): focal deletions and mutations; loss of SLIT-ROBO signaling may provide an alternative mechanism for activating oncogenic pathways PMID:23103869

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Loss of SLIT/ROBO signaling may influence efficacy of MET inhibitors in PDAC patients with ROBO1 loss; therapeutics targeting axon guidance molecules represent unexplored candidates PMID:23103869

Open questions

  • Functional validation of ROBO1 loss as a true driver (versus passenger) alteration in PDAC is incomplete; Sleeping Beauty transposon screen data are supportive but not definitive PMID:23103869

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:29622463

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