Comprehensive characteristics of somatic mutations in the normal tissues of patients with cancer and existence of somatic mutant clones linked to cancer development
| Autor: | Chang Ohk Sung, Ji-Hye Oh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Carcinogenesis Class I Phosphatidylinositol 3-Kinases Somatic cell DNA Mutational Analysis Mutant Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Germline mutation Neoplasms Exome Sequencing Genetics medicine Humans Gene Genetics (clinical) PI3K/AKT/mTOR pathway Exome sequencing Mutation Cancer medicine.disease 030104 developmental biology Organ Specificity 030220 oncology & carcinogenesis Cancer research Female |
| Zdroj: | Journal of Medical Genetics. 58:433-441 |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | BackgroundSomatic mutations are a major driver of cancer development and many have now been identified in various cancer types, but the comprehensive somatic mutation status of the normal tissues matched to tumours has not been revealed.MethodWe analysed the somatic mutations of whole exome sequencing data in 392 patient tumour and normal tissue pairs based on the corresponding blood samples across 10 tumour types.ResultsMany of the mutations involved in oncogenic pathways such as PI3K, NOTCH and TP53, were identified in the normal tissues. The ageing-related mutational signature was the most prominent contributing signature found and the mutations in the normal tissues were frequently in genes involved in late replication time (pPIK3CA mutations were identified in 6 normal tissues and were harboured by all of the matched cancer tissues. Multiple types of PIK3CA mutations were found in normal breast and matched cancer tissues. The PIK3CA mutations exclusively present in normal tissue may indicate clonal expansions unrelated to the tumour. In addition, PIK3CA mutation was appeared that they arose before the occurrence of the allelic imbalance.ConclusionOur current results suggest that somatic mutant clones exist in normal tissues and that their clonal expansion could be linked to cancer development. |
| Databáze: | OpenAIRE |
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