Cohesin Gene Mutations Linked to Mesothelioma Recurrence After Surgery

Researchers have identified mutations in a family of genes called the cohesin complex that are significantly more common in people whose multicystic peritoneal mesothelioma returned after surgery and heated intraperitoneal chemotherapy (HIPEC). The study, published in the British Journal of Cancer in March 2026, is the first to connect specific molecular changes to recurrence in this rare subtype of the disease.

The findings could eventually help oncologists identify which patients are at the highest risk of recurrence and point toward new drug targets for a cancer that currently has few treatment options beyond surgery.

What the Study Found

The research team used whole-exome sequencing to analyze tumor samples from people with multicystic mesothelioma who had undergone cytoreductive surgery (CRS) and HIPEC, the standard combined treatment approach. They compared the mutations found in tumors that recurred with those in tumors that did not.

Mutations in cohesin complex genes, particularly SMC3 and SMC1A, were significantly enriched in the recurrent tumors. The cohesin complex is a ring-shaped protein structure that holds DNA strands together during cell division and plays a role in gene regulation and DNA repair. When these genes are mutated, the resulting genomic instability may help tumors survive treatment and grow back.

Why Multicystic Mesothelioma Is Challenging

Multicystic mesothelioma, also called multicystic peritoneal mesothelioma (MCM), forms cystic lesions on the peritoneal lining of the abdomen. It is rarer than the more common pleural mesothelioma and distinct from the diffuse malignant form. While sometimes classified as borderline or low-grade, MCM can recur aggressively after treatment.

The standard approach combines CRS, in which surgeons remove as much visible tumor as possible, with HIPEC, which bathes the abdominal cavity in heated chemotherapy. Recurrence rates remain high, and until this study, no molecular markers had been identified to predict which patients would relapse.

The most commonly mutated genes in peritoneal mesothelioma overall are BAP1 (found in roughly 48% of cases), NF2, CDKN2A, and PBRM1. Cohesin mutations represent a new and separate pathway that may operate independently.

What This Means for Treatment

The authors call for further investigation, including laboratory models and clinical trials, to determine whether cohesin mutations could serve as biomarkers to guide treatment decisions. If validated in larger studies, testing for SMC3 and SMC1A mutations could help identify patients who may benefit from more aggressive post-surgical monitoring or alternative therapies.

Drugs targeting the cohesin pathway are in early development for other cancers. Whether those approaches could apply to mesothelioma remains an open question, but the identification of a specific molecular vulnerability is a necessary first step.