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Review
. 2021 Jun 24:11:695770.
doi: 10.3389/fonc.2021.695770. eCollection 2021.

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

Marion Grard  1   2 , Camille Chatelain  1   2 , Tiphaine Delaunay  1   2 , Elvire Pons-Tostivint  1   2   3 , Jaafar Bennouna  1   2   3 , Jean-François Fonteneau  1   2
Affiliations
Review

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

Marion Grard et al. Front Oncol. .

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.

Keywords: CDKN2A (p16); STING; homozygous deletion; immunotherapy; lung cancer; mesothelioma; type I interferon.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Homozygous Deletions in the p21.3 region of chromosome 9 in MPM and NSCLC. (A) Schematic representation of genes present in the p21.3 region of chromosome 9 between positions 21,000,000 and 22,200,000 drawn from UCSC Genome Browser (https://genome.ucsc.edu/). (B) Oncoprint representation of CDKN2A, CDKN2B, MTAP, IFNA2 and IFNB1 genomic alterations found in tumor samples of 82 MPM patients. Oncoprint was performed with cbioportals website (http://www.cbioportal.org/) using TCGA Pancancer atlas data. (C) Oncoprint representation of CDKN2A, CDKN2B, MTAP, IFNA2 and IFNB1 genomic alterations found in tumor samples of 1144 NSCLC patients. Oncoprint was performed with cbioportals website (http://www.cbioportal.org/) using TCGA Pan lung cancer data. Only the patients with at least one genomic alteration in the five genes are shown. ADC, adenocarcinoma; SqCC, squamous cell carcinoma.
Figure 2
Figure 2
The IFN I response. (1) The IFN I response is triggered by different stimuli such as ssDNA, dsDNA, ssRNA and dsRNA via the toll like receptors, the MAVS and the STING pathway. (2) Activation of these pathways induces the nuclear translocation of transcription factors such as IRF3, IRF7 and NF-kB that trigger IFN I production and expression of some interferon stimulated genes (ISGs). (3) Secreted IFN I trigger IFNAR signaling on neighboring cells, notably immune cells. (4) IFN I and other soluble factors of the IFN I response activate the immune response. (5) Activation of IFNAR signaling by IFN I leads to the formation of the interferon stimulated gene factor 3 complex. (6) This complex translocates to the nucleus and activates numerous ISGs with antiviral, immunomodulatory and regulatory functions. PRR, pattern recognition receptors.
See this image and copyright information in PMC

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