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Exon Sequence Analysis of the ATG5, ATG12, ATG9B Genes in Colorectal Cancer Patients During Radiotherapy

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Abstract

Radiotherapy (RT) which is a treatment regime for cancer patients may cause genetic instability and side effects. Etiological associations exist amongst autophagy-related gene (ATG) mutation and cancer. RT increases the rate of autophagy previously proven in vitro. The aforementioned background diverted us to conduct exon mutation analysis for ATG5, ATG12, and ATG9B genes of colorectal cancer patients who were receiving neoadjuvant RT. Peripheral blood DNA from different time points (before/middle/after RT) of the same patients was isolated and most tandem repeat-containing exons of ATG5, ATG12, and ATG9B were polymerase chain reaction-amplified and examined for mutations by Sanger sequencing. CA19-9/CEA (Tumor marker of colorectal cancer/Carcinoembryonic Antigen) serum levels were retrieved from the clinic. No exon variations detected for ATG5 and ATG12 genes. However, 4 patients (17.4%) showed frameshift mutation for ATG9B gene. Exon variation analysis of 2 (8.7%) patients resulted in GGG deletion at 8G mononucleotide tandem repeat region of ATG9B. Assigning patients as before RT and after RT, CA19-9 levels in ATG9B (Mutation) patients were higher compared to ATG9B (Wild Type) patients. ATG9B is highly likely to mutate during RT and ATG9B mutation correlates to higher CEA and CA19-9 levels and patients show poor prognosis.

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Funding

This study was supported by Istanbul University, Scientific Research, Project Unit. Project Number: TDK-21011.

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Authors and Affiliations

  1. Aziz Sancar Institute of Experimental Medicine, Department of Molecular Medicine, Istanbul University, Topkapi, Gureba Hospital Street, Number: 69, 34093, Fatih/Istanbul, Turkey

    Tuğba Mehmetoğlu Gürbüz, Şermin Durak, Faruk Çelik & Ş. Ümit Zeybek

  2. Institute of Oncology, Department of Radiation Oncology, Istanbul University, Istanbul, Turkey

    Ethem Nezih Oral & Rabia Nergiz Dağoğlu Sakin

  3. Institute of Oncology, Diagnostic Treatment and Care Services, Istanbul University, Istanbul, Turkey

    Şule Karaman

  4. Medical Faculty, Department of Medical Biology, Istanbul Yeni Yüzyıl University, Istanbul, Turkey

    Saadet Büşra Aksoyer Sezgin

  5. Istanbul Faculty of Medicine, Department of General Surgery, Istanbul, Turkey

    Metin Keskin

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Correspondence to Ş. Ümit Zeybek.

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Mehmetoğlu Gürbüz, T., Oral, E.N., Dağoğlu Sakin, R.N. et al. Exon Sequence Analysis of the ATG5, ATG12, ATG9B Genes in Colorectal Cancer Patients During Radiotherapy. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-023-01177-6

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