Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report

Irene Vanni, Simona Coco, Silvia Bonfiglio, Davide Cittaro, Carlo Genova, Federica Biello, Marco Mora, Valeria Rossella, Maria Giovanna Dal Bello, Anna Truini, Barbara Banelli, Dejan Lazarevic, Angela Alama, Erika Rijavec, Giulia Barletta, Francesco Grossi

Research output: Contribution to journalArticle

Abstract

The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient. Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM). Whole exome sequencing (WES) of the 3 tumors and of germline DNA was performed to determine the clonal origin and identify genetic cancer susceptibility. Both lung cancers were characterized by a high mutational rate with distinct mutational profiles and activation of tumor-specific pathways. Conversely, the PM harbored a relative low number of genetic variants and a novel mutation in the WT1 gene that might be involved in the carcinogenesis of nonasbestos-related mesothelioma. Finally, WES of the germinal DNA displayed several single nucleotide polymorphisms in DNA repair genes likely conferring higher cancer susceptibility. Overall, WES did not disclose any somatic genetic variant shared across the 3 tumors, suggesting their clonal independency; however, the carcinogenic effect of smoke combined with a deficiency in DNA repair genes and the patient advanced age might have been responsible for the MPT development. This case highlights the WES importance to define the clonal origin of MPT and susceptibility to cancer.

Original languageEnglish
Pages (from-to)e5447
JournalMedicine (United States)
Volume95
Issue number48
DOIs
Publication statusPublished - 2016

Keywords

  • Clonal origin
  • Mesothelioma
  • Multiple lung cancers
  • Tumor susceptibility
  • Whole exome sequencing

ASJC Scopus subject areas

  • Medicine(all)

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    Vanni, I., Coco, S., Bonfiglio, S., Cittaro, D., Genova, C., Biello, F., Mora, M., Rossella, V., Dal Bello, M. G., Truini, A., Banelli, B., Lazarevic, D., Alama, A., Rijavec, E., Barletta, G., & Grossi, F. (2016). Whole exome sequencing of independent lung adenocarcinoma, lung squamous cell carcinoma, and malignant peritoneal mesothelioma: A case report. Medicine (United States), 95(48), e5447. https://doi.org/10.1097/MD.0000000000005447