Homozygous Co-Deletion of Type I Interferons and CDKN2A Genes in Thoracic Cancers: Potential Consequences for Therapy

Our plain-English summary of Homozygous Co-Deletion of Type I Interferons and CDKN2A Genes in Thoracic Cancers: Potential Consequences for Therapy, by M. Grard, C. Chatelain, T. Delaunay, et al (Frontiers in Oncology, 2021).

The study

• Authors: M. Grard, C. Chatelain, T. Delaunay, E. Pons-Tostivint, J. Bennouna, J.F. Fonteneau
• Journal: Frontiers in Oncology
• Published: 2021;11:695770
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Homozygous deletion (HD) of the tumor suppressor gene CDKN2A is the most frequent genetic alteration in malignant pleural mesothelioma and is also frequent in non-small cell lung cancers. This HD is often accompanied by the HD of the type I interferons (IFN I) genes that are located closed to the CDKN2A gene on the p21.3 region of chromosome 9. IFN I genes encode sixteen cytokines (IFN-α, IFN-β…) that are implicated in cellular antiviral and antitumor defense and in the induction of the immune response. In this review, we discuss the potential influence of IFN I genes HD on thoracic cancers therapy and speak in favor of better taking these HD into account in patients monitoring.

Copyright © 2021 Grard, Chatelain, Delaunay, Pons-Tostivint, Bennouna and Fonteneau.

In plain English

This mini review looked at research on a genetic change in two chest cancers: malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). The change is the loss of both copies of the CDKN2A gene, often together with nearby type I interferon (IFN I) genes, which help defend cells against viruses and tumors. The authors noted that MPM is mainly due to asbestos exposure, but the review did not study asbestos. Earlier FISH studies had found CDKN2A loss in 60 to 80% of MPM patients. In the authors' own earlier work, 18 of 78 cultured MPM cell lines (23%) had lost IFNB1. A large database found losses of CDKN2A in 21% and of IFNB1 in 7% of 1,144 NSCLC patients. One cited study found significantly worse disease-free survival in NSCLC patients who had lost both gene groups than in those who had lost only CDKN2A. The authors' earlier lab work linked IFN I gene loss to sensitivity of MPM cell lines to an attenuated measles virus. The authors concluded that IFN I gene loss should be studied and taken into account in monitoring these 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: Mini review of published literature (no new patient data)
• Who was studied: Published studies and database analyses (The Cancer Genome Atlas, TCGA) of malignant pleural mesothelioma and non-small cell lung cancer patients and cell lines, including the authors' own earlier work
• Exposure: Not an exposure study. Asbestos is mentioned only as background: the article says MPM is mainly due to asbestos exposure. The subject is homozygous deletion of CDKN2A and type I interferon genes on chromosome 9.
• Main results:
  • The review reported that FISH studies found CDKN2A homozygous deletion in 60 to 80% of MPM patients, while the TCGA study reported 44%. The authors suggest the TCGA figure is lower because the biopsies contained non-malignant cells.
  • In the authors' earlier study of 78 short-term cultured MPM cell lines, 57 (73%) had CDKN2A deletion and 18 (23%) had IFNB1 deletion. In TCGA data on 82 MPM patients, the figures were 44% and 9%.
  • In the TCGA study of 1,144 NSCLC patients, 21% had CDKN2A gene deletion and 7% had IFNB1 gene deletion.
  • One cited study (Ye et al.) found that NSCLC patients who had lost both the IFN I and CDKN2A genes had significantly worse disease-free survival than patients who had lost only CDKN2A.
  • In the authors' earlier work on 22 MPM cell lines, 15 allowed the attenuated measles virus to replicate and destroy them. Of these, 11 could not produce IFN I, and 8 of those 11 had lost both copies of the IFN I genes.
• The authors' conclusion: The authors concluded that loss of IFN I genes should be studied and taken into account in monitoring MPM and NSCLC patients. They expect this would likely lead to new strategies and improvements in immunotherapy.
• Limitations the authors state:
  • Tumor biopsies such as those in the TCGA study contain non-malignant cells, which may hide deletions present only in tumor cells.
  • Apart from one study (Ye et al.), nothing is known about the prognostic value of IFN I gene loss, or its potential as an immunotherapy marker, in NSCLC, MPM and other cancers.
  • The studies reviewed do not clearly establish that IFN I production by the tumor cells themselves is required.

Topics

Medical terms in this study, explained in our Lexicon: CDKN2A, Homozygous Deletion, Tumor Suppressor Gene, Pleural Mesothelioma, Non-Small Cell Lung Cancer, Cytokine.

Related studies

• Frequent Homozygous Deletions of Type I Interferon Genes in Pleural Mesothelioma Confer Sensitivity to Oncolytic Measles Virus — T. Delaunay, C. Achard, et al. (2020)
• Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma — Q. Hu, S. Akatsuka, et al. (2010)
• Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report — K. Minami, N. Jimbo, et al. (2020)
• Homozygous deletion of CDKN2A in malignant mesothelioma: Diagnostic utility, patient characteristics and survival in a UK mesothelioma centre — K. Marshall, S. Jackson, et al. (2020)
• Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats — Y. Okazaki, N. Misawa, et al. (2020)
• Immunohistochemical Loss of MTAP as a Diagnostic and Prognostic Surrogate of CDKN2A/B Homozygous Deletion: A Narrative Review — S. Salzano, R. Caltabiano, et al. (2026)

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