For decades, mesothelioma has been understood as a single disease with a single cause: asbestos exposure. The diagnosis came with a predictable prognosis—median survival of 12 to 18 months, with few patients surviving beyond five years.
New research from the University of Hawaii Cancer Center challenges this understanding. Dr. Michele Carbone and his team have identified a fundamentally different form of mesothelioma—one caused by genetics rather than asbestos, and one that behaves far less aggressively than the conventional disease.
The discovery, published in the Journal of Thoracic Oncology in September 2025, could transform how mesothelioma is diagnosed, classified, and treated. For patients with this genetic form, the prognosis is dramatically better than for those with asbestos-related disease.
L-BAM: A New Category
The researchers have named the genetic variant L-BAM: Low-grade BAP1-Associated Mesothelioma. The name reflects its key characteristics:
Low-grade: Unlike typical mesothelioma, which grows aggressively and resists most treatments, L-BAM often progresses slowly. Tumors may remain stable for years without causing significant symptoms.
BAP1-Associated: The disease results from inherited mutations in the BAP1 gene—a tumor suppressor gene that, when inactivated, allows cancer to develop.
Mesothelioma: The cancer still arises in the mesothelium, the membrane lining the lungs, abdomen, or heart. But its behavior is distinct enough to warrant separate classification.
This distinction matters because L-BAM patients respond differently to treatment and have dramatically different outcomes than patients with conventional mesothelioma.
The Research Behind the Discovery
Dr. Carbone’s work on BAP1 and mesothelioma spans more than 25 years. His team’s key milestones include:
2011: Discovery of the first gene responsible for familial mesothelioma, published in Nature Genetics. This established that inherited BAP1 mutations could cause mesothelioma in families with multiple affected members.
2017: Identification of the mechanisms responsible for BAP1’s tumor suppressor activity, published in Nature. This work explained how BAP1 mutations allow cancer to develop.
2020-2024: Discovery of additional genes that may cause mesothelioma when mutated, published in PNAS. This expanded understanding of genetic risk factors.
2025: The L-BAM classification, formalizing the distinct clinical entity and its implications for patient care.
The Data
The September 2025 publication describes findings from a large cohort of individuals with inherited BAP1 mutations:
238 carriers of germline BAP1 mutations, aged 27 to 81, were followed over time.
84 developed mesothelioma (35% of carriers)—a rate dramatically higher than the general population but lower than might be expected if the mutation guaranteed cancer.
Only 1 of the 84 mesothelioma patients had evidence of significant asbestos exposure. This finding suggests that BAP1 mutation alone, without asbestos, can cause mesothelioma—a radical departure from conventional understanding.
123 siblings and relatives who did not inherit the BAP1 mutation were also followed. None developed mesothelioma, demonstrating that the mutation, not shared environmental exposure, drove cancer development.
45.2% of L-BAM patients developed multiple cancers, including melanoma, kidney cancer, breast cancer, and liver cancer. This indicates that BAP1 mutation creates susceptibility to various malignancies, not just mesothelioma.
Different Biology, Different Outcomes
The most important clinical finding is that L-BAM behaves fundamentally differently than asbestos-related mesothelioma:
| Characteristic | Conventional Mesothelioma | L-BAM |
|---|---|---|
| Cause | Asbestos exposure | BAP1 gene mutation |
| Growth rate | Aggressive | Often slow/indolent |
| Treatment response | Generally poor | Often responds well |
| Median survival | 12-18 months | Potentially near-normal lifespan |
| Age at diagnosis | Typically 60s-70s | Can be younger (starting at 27 in study) |
The researchers report that L-BAM tumors may remain stable for years. During this early, indolent phase, patients may not require aggressive therapy. This represents a dramatic shift from the “treat immediately and aggressively” approach that conventional mesothelioma demands.
If you’ve been diagnosed with mesothelioma—especially without clear asbestos exposure history—ask about BAP1 testing. If you carry the mutation, you may have L-BAM with different treatment options and dramatically better prognosis than conventional disease. Family members may also benefit from genetic counseling.
Clinical Implications
The discovery has several immediate implications for patient care:
Genetic testing: Patients diagnosed with mesothelioma, especially those without clear asbestos exposure history, should be tested for BAP1 mutations. Those with L-BAM may have different treatment options and prognoses than those with conventional disease.
Family screening: Because BAP1 mutations are inherited, family members of L-BAM patients may also carry the mutation. Genetic screening can identify at-risk individuals before cancer develops.
Surveillance protocols: Carriers of BAP1 mutations need regular monitoring for multiple cancer types—not just mesothelioma, but also melanoma, kidney cancer, and other malignancies.
Treatment decisions: L-BAM patients may not need immediately aggressive treatment. In some cases, active surveillance may be appropriate until the tumor shows signs of progression.
The Debate
Not all researchers fully agree with the implications of Carbone’s findings. Some have argued that BAP1 mutation makes people more susceptible to asbestos’s carcinogenic effects, rather than causing mesothelioma independently.
Dr. Hedy Kindler, Director of the Multidisciplinary Mesothelioma Program at the University of Chicago, has stated: “These genes, particularly BAP1, will make patients more sensitive to the carcinogenic effects of asbestos… rather than serving as a direct cause of mesothelioma.”
The debate has practical implications. If BAP1 mutation is an independent cause, then carriers should be monitored regardless of asbestos exposure history. If BAP1 simply increases susceptibility to asbestos, then exposure history remains the key factor in assessing risk.
The Hawaii researchers counter that their data showing mesothelioma in carriers without asbestos exposure supports an independent causative role. The scientific discussion continues.
Ongoing Clinical Trials
The discovery of L-BAM has led to clinical trials testing new treatment approaches. The National Cancer Institute is conducting two protocols:
NCT05960773: Testing whether oral epigenetic agents can prevent progression of early L-BAM tumors in patients with BAP1 Cancer Syndrome.
NCT06654050: Further investigating targeted treatments for patients with BAP1 mutations.
These trials represent a new paradigm: treating mesothelioma based on its genetic cause rather than simply its location in the body. If successful, they could provide L-BAM patients with treatments specifically designed for their biology.
Implications for Mesothelioma Understanding
The L-BAM discovery challenges the longstanding assumption that mesothelioma equals asbestos. While asbestos remains the primary cause of the disease—responsible for the vast majority of cases—genetics now appears to play a larger role than previously recognized.
This has implications for:
Legal proceedings: If some mesothelioma cases result from genetics rather than asbestos exposure, establishing causation in litigation becomes more complex. Defendants may argue that plaintiff’s disease was genetic rather than exposure-related.
Screening programs: Identifying BAP1 mutation carriers could enable monitoring before cancer develops. Unlike asbestos-related mesothelioma, which cannot currently be detected before symptoms appear, genetic testing can identify at-risk individuals decades in advance.
Research direction: Understanding why L-BAM behaves less aggressively than conventional mesothelioma could provide insights into making all mesothelioma more treatable.
For Patients and Families
If you have been diagnosed with mesothelioma, this research suggests several considerations:
Ask about genetic testing, especially if you have no clear history of asbestos exposure or if you have family members who also developed mesothelioma or other cancers.
If you carry a BAP1 mutation, discuss with your medical team whether you might have L-BAM and what that means for your treatment plan.
If you have relatives with mesothelioma, consider genetic counseling to assess whether BAP1 testing might be appropriate for your family.
If you are a BAP1 carrier, work with your doctors to establish a surveillance program for multiple cancer types, not just mesothelioma.
The Larger Picture
Dr. Carbone’s 25-year research journey from discovering the BAP1 connection to defining L-BAM as a distinct entity represents how science gradually improves understanding of complex diseases.
Mesothelioma is not one disease. It is a category that includes biologically distinct conditions with different causes, behaviors, and outcomes. The recognition of L-BAM as a separate entity is likely just the beginning—future research may identify additional subtypes based on genetics, molecular markers, or other factors.
For patients diagnosed today, this matters. A diagnosis of “mesothelioma” no longer tells the complete story. The specific type—whether genetic or asbestos-related, epithelioid or sarcomatoid, early or advanced—determines prognosis and shapes treatment decisions.
The L-BAM discovery offers hope that mesothelioma, long considered uniformly lethal, may include forms that can be effectively managed for years or decades. It also offers a roadmap for research: understanding why some mesotheliomas are less deadly could reveal strategies for making all forms more treatable.
What is L-BAM?▼
L-BAM (Low-grade BAP1-Associated Mesothelioma) is a genetic form of mesothelioma caused by inherited BAP1 gene mutations rather than asbestos exposure. Unlike conventional mesothelioma (12-18 month median survival), L-BAM often progresses slowly and patients may live nearly normal lifespans with appropriate treatment.
How do I know if I have L-BAM vs conventional mesothelioma?▼
Genetic testing for BAP1 mutations can identify L-BAM. Consider testing especially if you have no clear asbestos exposure history, family members with mesothelioma or other cancers, or were diagnosed younger than typical (study patients ranged 27-81 years).
What does this mean for my family?▼
BAP1 mutations are inherited. If you carry the mutation, family members may also be at risk—not just for mesothelioma, but for melanoma, kidney cancer, and other malignancies (45% of L-BAM patients developed multiple cancers). Genetic counseling can help assess family risk and establish surveillance protocols.
Does this change asbestos litigation?▼
Potentially. If some mesothelioma is genetic rather than asbestos-related, establishing causation in litigation becomes more complex. However, L-BAM appears to be a minority of cases—asbestos remains the primary cause for most mesothelioma diagnoses.