Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan

Our plain-English summary of Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan, by J.A. Gibson, K.E. Finberg, I. Nalbantoglu, et al (The Lancet. Oncology, 2021).

The study

• Authors: J.A. Gibson, K.E. Finberg, I. Nalbantoglu, M. Cecchini, A. Ganzak, Z. Walther, J.L. Sklar, J.P. Eder, S.B. Goldberg
• Journal: The Lancet. Oncology
• Published: 2021;22(3):306-307
• Type of article: Case report
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article is a case report from the Yale Cancer Center Precision Medicine Tumor Board in the USA, describing one patient. A 63-year-old man had his gallbladder removed for gallstones, and tumour cells were found in its outer lining. He was first diagnosed with poorly differentiated adenocarcinoma of unknown primary, and scans and endoscopy found no primary site. Further staining suggested the tumour came from mesothelial cells. Gene sequencing of the tumour and of his blood found a harmful variant in the BAP1 gene in both, consistent with an inherited (germline) variant. A second BAP1 variant was found only in the tumour. The diagnosis was revised to malignant mesothelioma, and he was diagnosed with BAP1 tumour predisposition syndrome. His treatment plan changed to debulking surgery followed by chemotherapy given into the abdomen, and surgery confirmed primary peritoneal mesothelioma. The authors concluded that detecting the BAP1 variants was crucial in confirming this diagnosis. They also concluded that pairing tumour testing with blood testing was valuable. The article does not discuss asbestos exposure.

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 (single patient)
• Who was studied: One 63-year-old man referred to Yale Cancer Center (New Haven, CT, USA) after cancer was found in his removed gallbladder
• Exposure: The article does not mention asbestos exposure. It concerns an inherited (germline) variant in the BAP1 gene, found by sequencing tumour and blood DNA.
• Main results:
  • The patient was initially diagnosed with poorly differentiated adenocarcinoma of unknown primary.
  • Further staining of the tumour cells was consistent with mesothelial origin rather than adenocarcinoma.
  • A BAP1 nonsense variant was found in both the tumour and the blood, at allelic fractions close to 50% (table: 50% in tumour, 55% in blood). This was compatible with a heterozygous germline (inherited) variant.
  • A second, pathogenic BAP1 frameshift variant was found in the tumour only, at an allelic fraction of 11% (0% in blood). This was compatible with a somatic second mutation.
  • The diagnosis was revised to malignant mesothelioma, and BAP1 tumour predisposition syndrome (BAP1-TPDS) was diagnosed after genetic counselling.
  • The revised diagnosis changed the treatment plan to abdominal debulking surgery followed by intraperitoneal chemotherapy. Exploratory surgery confirmed primary peritoneal mesothelioma.
  • Review of the patient's records found a basal cell carcinoma, another BAP1-TPDS-associated tumour, 2 years earlier.
  • Several first-degree relatives had a history of cancer, but no confirmed BAP1-TPDS-associated cancers were identified in the family.
• The authors' conclusion: The authors concluded that detecting the BAP1 variants was crucial in confirming a rare, unexpected diagnosis of primary peritoneal mesothelioma that had first been misclassified as adenocarcinoma. They also concluded that the germline finding had consequences for the patient's surveillance and potential implications for family members.
• Limitations the authors state:
  • The sequencing could not show whether the two BAP1 mutations were on the same or different copies of the gene. The authors assumed both copies were mutated.
  • The role of the SETD2 variant found in the tumour is unclear.

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: Tumor Board.

Related studies

• Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies — T.K. Hinz, L.E. Heasley (2020)
• Gender differences in molecular-guided therapy recommendations for metastatic malignant mesothelioma — H. Taghizadeh, S. Zöchbauer-Müller, et al. (2020)
• A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma — J. Lai, Z. Zhou, et al. (2016)
• Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine — L. Ye, S. Ma, et al. (2019)
• Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma — T. Naka, Y. Hatanaka, et al. (2016)
• Molecular pathways and diagnosis in malignant mesothelioma: A review of the 14th International Conference of the International Mesothelioma Interest Group — D.B. Chapel, A. Churg, et al. (2019)

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