Cohesin Gene Mutations Linked to Mesothelioma Recurrence After Surgery
Genomic study finds SMC3 and SMC1A mutations in multicystic peritoneal mesothelioma predict disease recurrence after cytoreductive surgery and HIPEC.
Researchers at the University of Southampton 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). In March 2026, the British Journal of Cancer published the study, the first to connect specific molecular changes to recurrence in this rare subtype of the disease. Led by Jane Gibson and N.J. Carr, the work came from the university’s Cancer Sciences unit in the Faculty of Medicine, which applies genomic and molecular profiling to define the drivers of cancer development and progression, including alterations that may influence mesothelioma behavior and recurrence.
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.
People diagnosed with multicystic peritoneal mesothelioma can ask their oncologist about genomic profiling of their tumor. Tests like whole-exome sequencing or targeted gene panels may reveal mutations that affect prognosis or treatment planning. The 2026 clinical trials landscape includes trials for peritoneal mesothelioma.
References
British Journal of Cancer. (2026-03-14). Genomic sequencing of multicystic mesothelioma finds cohesin complex mutations associated with disease recurrence in patients referred for cytoreductive surgery and HIPEC.
https://doi.org/10.1038/s41416-026-03366-5
Reader Q&A
Frequently Asked Questions
What is multicystic peritoneal mesothelioma?
What is the cohesin complex?
Can this study change how multicystic mesothelioma is treated?
Is multicystic mesothelioma caused by asbestos?
How close are we to a cure for mesothelioma?
No cure exists for mesothelioma as of 2026. Approved first-line treatments include nivolumab plus ipilimumab immunotherapy (FDA-approved, with 3-year PFS of 14% vs. 1% for chemotherapy) and pembrolizumab plus chemotherapy (ORR 22% vs. 6%). Over 80 active clinical trials test emerging therapies like enzyme therapy (ADI-PEG20 extended survival 4-fold at 3 years), cancer vaccines (UV1 doubled response rates), and targeted therapies, with median survival reaching 18+ months in some multimodal approaches. Research shows improved outcomes but no evidence of curative potential yet.
How did Steve McQueen get mesothelioma?
Steve McQueen was exposed to asbestos through multiple occupational and military sources over several decades. His primary exposure occurred during his service in the U.S. Marine Corps from 1947 to 1950, when he worked aboard naval ships and in shipyards, including removing asbestos lagging from pipes at Camp Lejeune. After his military service, he encountered additional asbestos exposure on movie soundstages where insulation contained the mineral, while wearing flame-resistant racing suits made with asbestos, and while working on race car and motorcycle brakes. McQueen did not develop symptoms until 1978, nearly 30 years after his initial military exposure, reflecting the typical latency period of 20 to 50 years between asbestos exposure and mesothelioma diagnosis. He was diagnosed with pleural mesothelioma in December 1979 and died in November 1980 at age 50.
Is mesothelioma 100% fatal?
Mesothelioma has a very poor prognosis, with a median survival of approximately one year from diagnosis and a five-year survival rate of 10-12%. However, it is not universally 100% fatal. Some people with mesothelioma have survived for extended periods with multimodal treatment (surgery, chemotherapy, and radiation), and survival outcomes vary significantly based on cancer stage, histological type, and individual response to treatment. Peritoneal mesothelioma, for example, shows better one-year survival rates (92%) compared to pleural mesothelioma (approximately 40% 1-year survival per SEER), suggesting that type and early detection can influence outcomes. While the disease remains highly aggressive and fatal in the majority of cases, advances in treatment protocols continue to improve survival rates incrementally.