Malignant Peritoneal Mesothelioma in an Infant With Familial ATM Mutations

Our plain-English summary of Malignant Peritoneal Mesothelioma in an Infant With Familial ATM Mutations, by A. Mijalovsky, D. Halperin, Y. Perez, et al (Journal of Pediatric Hematology/oncology, 2018).

The study

• Authors: A. Mijalovsky, D. Halperin, Y. Perez, B. Zafarov, R. Shaco-Levy, J. Kapelushnik, H. Flusser, O.S. Birk
• Journal: Journal of Pediatric Hematology/oncology
• Published: 2018;40(8):e511-e515
• Type of article: Case report
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Ataxia-telangiectasia (A-T), an autosomal recessive disorder characterized by progressive neurologic dysfunction, oculocutaneous telangiectasia, immunodeficiency, and cancer susceptibility, is caused by mutations in the ATM gene. A previous study of 4 A-T patients identified 2 rare homozygous missense mutations residing on the same allele of the ATM gene: c.1514T>C and c.1547T>C, which were shown to decrease ATM levels and increase T-cell acute lymphoblastic leukemia predisposition. We studied 5 patients from 2 consanguineous Bedouin families of the same tribe, presenting with A-T. Whole-exome sequencing data identified the 2 aforementioned mutations in ATM, which segregated within all family members as expected of autosomal recessive heredity. Interestingly, one individual was diagnosed with malignant peritoneal mesothelioma (MPM), an extremely rare neoplasm in pediatric patients. Here, we describe a case of a 4-month-old infant homozygous for the 2 ATM mutations, who developed MPM and died by the age of 2 years. To the best of our knowledge, this is the first case of peritoneal mesothelioma in an infant bearing ATM mutations, and one of the youngest pediatric mesotheliomas described. Thus, the risk of MPM might be considered in the follow-up of A-T patients, and ATM mutations sought in cases of early-onset MPM.

In plain English

This case report came from a genetic study of 12 members of two related, consanguineous Bedouin families of one tribe in Israel, five of whom had a mild form of the inherited disorder ataxia-telangiectasia (A-T). One infant was diagnosed at 4 months with malignant peritoneal mesothelioma, a cancer of the abdominal lining, and died by age 2. A large abdominal mass was removed surgically, and the first biopsy was read as benign cystic mesothelioma. At 17 months the infant returned with a severe relapse, received chemotherapy, and died of sepsis after a month in hospital. Two independent pathology institutes found the tumor consistent with malignant mesothelioma. DNA from the tumor tissue showed the infant carried two copies of the same two ATM gene mutations found in the family's A-T patients. The article reported no assessment of asbestos exposure. The authors regarded the ATM mutations as the most likely cause, but stated that further functional studies are needed to prove this. They suggested peritoneal mesothelioma risk might be considered in following A-T patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of one infant, within a family genetic study using homozygosity mapping, whole-exome sequencing and Sanger sequencing
• Who was studied: 12 members of 2 remotely related consanguineous Bedouin families of a single tribe, studied at Soroka Medical Center, Beer Sheva, Israel. Five were diagnosed with A-T, and 1 deceased infant was diagnosed with malignant peritoneal mesothelioma. Study dates are not given.
• Exposure: No asbestos or other mineral fiber exposure was studied or reported. The factor examined was genetic: two ATM gene mutations, c.1514T>C and c.1547T>C, carried in the homozygous state.
• Main results:
  • The infant (patient P-I, II:3) was diagnosed with malignant peritoneal mesothelioma at 4 months and died by the age of 2 years.
  • At 4 months, imaging showed a 14 by 17 by 5 cm intraperitoneal mass penetrating the liver, which was completely removed surgically.
  • The initial biopsy was read as benign cystic mesothelioma.
  • After a lack of follow-up, the infant returned at 17 months with a severe relapse.
  • The infant received chemotherapy and died of sepsis after a month of hospitalization.
  • Two independent pathology institutes, working double-blinded, found the tumor tissue consistent with malignant peritoneal mesothelioma.
  • DNA extracted from the infant's abdominal biopsy showed that the infant was homozygous for both familial ATM mutations.
  • The five A-T patients in the families had mild A-T.
  • No lymphomas or leukemias were found in any of the A-T patients.
  • The authors regarded the ATM mutations, rather than mineral or radiation exposure, as the most likely cause of this infant's mesothelioma.
• The authors' conclusion: The authors concluded that the risk of malignant peritoneal mesothelioma might be considered in the follow-up of A-T patients and in the differential diagnosis of children with A-T who have unexplained abdominal symptoms. They also suggested that ATM mutations might be relevant candidates in cases of early-onset malignant peritoneal mesothelioma.
• Limitations the authors state:
  • The authors stated that further functional studies are needed to prove that the ATM mutations actually cause malignant peritoneal mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Neoplasm, Mesothelioma.

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• Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy — M.G. White, J.J. Schulte, et al. (2021)
• Establishment and mutation analysis of a novel malignant peritoneal mesothelioma cell line, TU-MM-1, using whole genome sequencing — N. Oumi, H. Itamochi, et al. (2016)
• BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas — N. Leblay, F. Leprêtre, et al. (2017)
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