Hypoxia increases mutational load of breast cancer cells through frameshift mutations
| Autor: | Francis Amirtharaj, Kapaettu Satyamoorthy, Walid El-Sayed, Philippe Dessen, Raefa Abou Khouzam, Jerome Thiery, Filippo Rosselli, Goutham Hassan Venkatesh, Salem Chouaib, Husam Nawafleh, Sandeep Mallya, Pamela Bravo, Bartosz Wojtas |
|---|---|
| Přispěvatelé: | Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Intégrité du génome et cancers (IGC), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genome instability DNA repair DNA damage [SDV]Life Sciences [q-bio] Immunology Breast Neoplasms Biology Frameshift mutation 03 medical and health sciences 0302 clinical medicine Chromosome instability Immunology and Allergy Humans Frameshift Mutation Hypoxia Exome sequencing RC254-282 Original Research Point mutation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC581-607 Cell Hypoxia 3. Good health 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Immunologic diseases. Allergy mutational burden |
| Zdroj: | OncoImmunology OncoImmunology, Taylor & Francis, 2020, 9 (1), pp.1750750. ⟨10.1080/2162402X.2020.1750750⟩ OncoImmunology, Vol 9, Iss 1 (2020) Oncoimmunology |
| ISSN: | 2162-4011 2162-402X |
| Popis: | International audience; Tumor hypoxia-induced downregulation of DNA repair pathways and enhanced replication stress are potential sources of genomic instability. A plethora of genetic changes such as point mutations, large deletions and duplications, microsatellite and chromosomal instability have been discovered in cells under hypoxic stress. However, the influence of hypoxia on the mutational burden of the genome is not fully understood. Here, we attempted to elucidate the DNA damage response and repair patterns under different types of hypoxic stress. In addition, we examined the pattern of mutations exclusively induced under chronic and intermittent hypoxic conditions in two breast cancer cell lines using exome sequencing. Our data indicated that hypoxic stress resulted in transcriptional downregulation of DNA repair genes which can impact the DNA repair induced during anoxic as well as reoxygenated conditions. In addition, our findings demonstrate that hypoxic conditions increased the mutational burden, characterized by an increase in frameshift insertions and deletions. The somatic mutations were random and nonrecurring, as huge variations within the technical duplicates were recognized. Hypoxia also resulted in an increase in the formation of potential neoantigens in both cell lines. More importantly, these data indicate that hypoxic stress mitigates DNA damage repair pathways and causes an increase in the mutational burden of tumor cells, thereby interfering with hypoxic cancer cell immunogenicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|