MEN1

Overview

MEN1 encodes menin, a scaffold protein and component of the MLL/SET1-like histone methyltransferase complex that deposits H3K4 methylation marks at gene promoters. Germline MEN1 mutations cause Multiple Endocrine Neoplasia type 1 syndrome; somatic inactivating mutations are the most frequent genetic event in sporadic pancreatic neuroendocrine tumors (PanNETs). MEN1 functions as a tumor suppressor through epigenetic regulation of gene expression.

Alterations observed in the corpus

  • MEN1 was the most frequently mutated gene in PanNETs, with inactivating mutations (indels, nonsense, splice-site) in 44% of 68 tumors by exome sequencing; biallelic inactivation documented, consistent with classic two-hit tumor suppressor model PMID:21252315
  • Somatic mutation in 1/23 (4%) pancreatic acinar cell carcinomas; occurred in a mixed acinar-ductal carcinoma without neuroendocrine features PMID:24293293
  • Recurrent loss-of-function in pancreatic and pulmonary neuroendocrine neoplasms (PanNENs/PulNENs); PanNEN-specific large-scale LOH observed; MEN1 loss used to support cell-cycle and MTOR-inhibitor (everolimus) therapy recommendations in multiple patients PMID:24326773
  • MEN1 among tumor suppressor genes mutated in 15/402 (3.7%) PTC tumors in the TCGA thyroid cohort PMID:25417114
  • MEN1 truncating mutations observed at low frequency in PDTC and ATC as part of a set of infrequent truncating mutations alongside NF2 and RB1 PMID:26878173
  • MEN1 nominated as a breast cancer mutation-driver via combined homozygous deletion and inactivating-mutation evidence in 2,433-tumor whole-genome/exome sequencing study PMID:27161491

Cancer types (linked)

  • PANET: Inactivating MEN1 mutations in 44% of sporadic PanNETs; biallelic inactivation establishes MEN1 as the dominant tumor suppressor in this cancer type PMID:21252315

Co-occurrence and mutual exclusivity

  • MEN1 mutations co-occur with DAXX and ATRX mutations in PanNETs, forming an epigenetic mutation cluster; DAXX/ATRX alterations associated with alternative lengthening of telomeres (ALT) PMID:21252315

Therapeutic relevance

  • MEN1 loss may sensitize tumors to inhibitors of downstream epigenetic pathways; mTOR pathway inhibitors (everolimus) are approved for PanNETs, and MEN1-mutant tumors may have distinct pathway dependencies.

Open questions

  • The relationship between MEN1 loss and therapeutic response to somatostatin analogs or mTOR inhibitors in PanNETs is not fully characterized.

Sources

  • PMID:21252315 — Exome sequencing of pancreatic neuroendocrine tumors (PanNETs)

This page was processed by crosslinker on 2026-05-09. - PMID:24293293

This page was processed by crosslinker on 2026-05-09. - PMID:24326773

This page was processed by crosslinker on 2026-05-09. - PMID:25417114

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

This page was processed by wiki-cli on 2026-05-14. - PMID:27161491

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