Computer generated image of mesothelioma

Genetics and DNA Repair in Mesothelioma

General Audience

Dr. Churpek studies how inherited changes in a person’s genes might play a role in mesothelioma, a type of cancer often linked to asbestos exposure. She found that about 12 out of every 100 people with mesothelioma have an inherited genetic change in certain genes that help fix DNA damage. This means that genetics, not just asbestos, may increase someone’s risk for this cancer. In collaboration with other scientists, she also found that people with specific inherited genetic changes lived longer after treatment with a common type of chemotherapy used for this cancer.

Now, Dr. Churpek is working on figuring out how these gene changes might help doctors predict which treatments will work best. With support from the Department of Defense, she’s using advanced tools to look closely at the genes of people with mesothelioma. Her goal is to create a test that can show which patients are most likely to benefit from a specific type of chemotherapy. She aims to learn more about how this cancer looks and acts in people with inherited gene changes, so doctors can give them the best care possible.

Scientific Audience

Panou V, Gadiraju M, Wolin A, Weipert CM, Skarda E, Husain AN, Patel JD, Rose B, Zhang SR, Weatherly M, Nelakuditi V, Knight Johnson A, Helgeson M, Fischer D, Desai A, Sulai N, Ritterhouse L, Røe OD, Turaga KK, Huo D, Segal J, Kadri S, Li Z, Kindler HL, Churpek JE. Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma. J Clin Oncol. 2018 Oct 1;36(28):2863-2871. doi: 10.1200/JCO.2018.78.5204. Epub 2018 Aug 16. PMID: 30113886; PMCID: PMC6804864.

Dr. Churpek’s work explores the role of pathogenic inherited genetic variants in mesothelioma, a cancer traditionally linked to asbestos exposure. Her research identified that 12% of unselected mesothelioma patients carry an inherited pathogenic variant in one of 13 cancer susceptibility genes, most of which are involved in DNA repair pathways. This discovery suggests a broader genetic basis for mesothelioma, highlighting inherited genetic variants as risk factors in disease development and treatment outcomes. Additionally, patients with these inherited variants showed improved survival rates following platinum-based chemotherapy.

Building on these findings, Dr. Churpek is currently investigating how these genetic alterations can predict treatment responsiveness. This research is supported by a Department of Defense Award (W81XWH2110817), where she is using whole genome and RNA sequencing to assess the full spectrum of DNA repair-related genetic changes in mesothelioma. The goal is to develop a predictive model for platinum sensitivity that could be used in clinical practice. Dr. Churpek’s work also focuses on understanding the unique clinical characteristics of individuals with both mesothelioma and a germline pathogenic variant, aiming to refine patient management strategies.

Berger Y, Gadiraju M, Dhiman A, Gilliam K, Opalecky B, Chen H, Helgeson M, Eng OS, Husain AN, Drazer MW, Kindler HL, Churpek JE, Turaga KK. Surgical phenotype of patients with peritoneal mesothelioma and a germline mutation. Cancer. 2023 Jul 15;129(14):2152-2160. PubMed PMID: 37042570.
Carbone M, Pass HI, Ak G, Alexander HR Jr, Baas P, Baumann F, Blakely AM, Bueno R, Bzura A, Cardillo G, Churpek JE, Dianzani I, De Rienzo A, Emi M, Emri S, Felley-Bosco E, Fennell DA, Flores RM, Grosso F, Hayward NK, Hesdorffer M, Hoang CD, Johansson PA, Kindler HL, Kittaneh M, Krausz T, Mansfield A, Metintas M, Minaai M, Mutti L, Nielsen M, O’Byrne K, Opitz I, Pastorino S, Pentimalli F, de Perrot M, Pritchard A, Ripley RT, Robinson B, Rusch V, Taioli E, Takinishi Y, Tanji M, Tsao AS, Tuncer AM, Walpole S, Wolf A, Yang H, Yoshikawa Y, Zolondick A, Schrump DS, Hassan R. Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations. J Thorac Oncol. 2022 Jul;17(7):873-889. PubMed Central PMCID: PMC9233126.
Hassan R, Morrow B, Thomas A, Walsh T, Lee MK, Gulsuner S, Gadiraju M, Panou V, Gao S, Mian I, Khan J, Raffeld M, Patel S, Xi L, Wei JS, Hesdorffer M, Zhang J, Calzone K, Desai A, Padiernos E, Alewine C, Schrump DS, Steinberg SM, Kindler HL, King MC, Churpek JE. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):9008-9013. PubMed Central PMCID: PMC6500142.
Panou V, Gadiraju M, Wolin A, Weipert CM, Skarda E, Husain AN, Patel JD, Rose B, Zhang SR, Weatherly M, Nelakuditi V, Knight Johnson A, Helgeson M, Fischer D, Desai A, Sulai N, Ritterhouse L, Røe OD, Turaga KK, Huo D, Segal J, Kadri S, Li Z, Kindler HL, Churpek JE. Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma. J Clin Oncol. 2018 Oct 1;36(28):2863-2871. PubMed Central PMCID: PMC6804864.
Kindler HL, Ismaila N, Bazhenova L, Chu Q, Churpek JE, Dagogo-Jack I, Bryan DS, Drazer MW, Forde P, Husain AN, Sauter JL, Rusch V, Bradbury PA, Cho BCJ, de Perrot M, Ghafoor A, Graham DL, Khorshid O, Lebensohn A, White J, Hassan R. Treatment of Pleural Mesothelioma: ASCO Guideline Update. J Clin Oncol. 2025 Mar 10;43(8):1006-1038. doi: 10.1200/JCO-24-02425. Epub 2025 Jan 8. PMID: 39778125.

Papers in Plain Language

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