SPINK1

Overview

SPINK1 (Serine Peptidase Inhibitor, Kazal Type 1) encodes a serine protease inhibitor originally identified in pancreatic acinar cells. In prostate cancer, SPINK1 outlier overexpression defines a distinct molecular subtype of ETS fusion-negative tumors, accounting for approximately 10% of prostate cancers. SPINK1-positive tumors represent a separate oncogenic pathway from TMPRSS2:ERG or other ETS gene fusions.

Alterations observed in the corpus

  • SPINK1 outlier expression identified as a molecular subtype marker in prostate cancer WES of 112 tumors (Michigan cohort, 50 lethal CRPCs + 11 localized); SPINK1-positive status stratified alongside ETS gene fusions in the copy number and mutation heatmap analysis PMID:22722839
  • Overexpressed in MSK-PCa5 and MSK-PCa7 prostate cancer cell lines as an ETS-fusion-exclusive subtype marker in castration-resistant prostate cancer PMID:25201530
  • Frequently overexpressed in the SPOP-mutant/CHD1-deleted prostate cancer subtype; SPOP hotspot mutations (11%) define a subtype with SPINK1 overexpression and highest AR transcriptional output PMID:26544944

Cancer types (linked)

  • Prostate adenocarcinoma (PRAD): SPINK1 outlier expression defines an ETS fusion-negative subtype of prostate cancer, mutually exclusive with TMPRSS2:ERG and other ETS fusions PMID:22722839

Co-occurrence and mutual exclusivity

  • SPINK1 outlier expression is mutually exclusive with ETS gene fusions (e.g., TMPRSS2:ERG) in prostate cancer, defining separate molecular subtypes PMID:22722839

Therapeutic relevance

  • No direct targeted therapies identified for SPINK1-positive prostate cancer in the corpus. The distinct biology of SPINK1-positive tumors may require subtype-specific therapeutic strategies.

Open questions

  • The functional role of SPINK1 overexpression in prostate cancer initiation and progression remains incompletely understood.
  • Whether SPINK1-positive CRPCs have differential responses to androgen deprivation or chemotherapy compared to ETS fusion-positive tumors is not established in the corpus.

Sources

  • PMID:22722839 — Prostate cancer WES, 112 tumors, Michigan cohort

This page was processed by crosslinker on 2026-05-14. - PMID:25201530

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

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