DCC

Overview

DCC (Deleted in Colorectal Carcinoma) encodes a dependence receptor for netrin-1 that mediates axon guidance and is broadly regarded as a tumor suppressor. In the absence of its ligand, DCC induces apoptosis; netrin-1 binding suppresses this pro-apoptotic activity. Originally identified as a candidate tumor suppressor at 18q21 in colorectal cancer, DCC has since been implicated in other malignancies. In cutaneous melanoma, DCC is recurrently inactivated by somatic mutations and shows a positive statistical association with RAC1 P29S mutations, suggesting pathway-level cooperativity.

Alterations observed in the corpus

  • DCC inactivating mutations are identified in the Yale melanoma WES cohort of 147 tumors and show a positive association with RAC1 P29S mutations, suggesting cooperative selection in the same molecular subgroup of sun-exposed melanomas PMID:22842228

Cancer types (linked)

  • MEL (cutaneous melanoma): Inactivating mutations positively associated with RAC1 P29S; Yale WES cohort (147 tumors) PMID:22842228

Co-occurrence and mutual exclusivity

  • DCC mutations are positively associated with RAC1 P29S (gain-of-function) mutations in sun-exposed cutaneous melanoma PMID:22842228

Therapeutic relevance

  • No direct targeted therapy for DCC loss established; the association with RAC1 P29S may indicate relevance to RAC1/PAK pathway inhibition strategies in melanoma PMID:22842228

Open questions

  • Whether DCC loss provides functional cooperativity with RAC1 P29S through convergent cytoskeletal or apoptotic pathway effects, or reflects a statistical association driven by UV mutational signature, remains unresolved.

Sources

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