Host Genome Variation is Associated with Neurocognitive Outcome in Survivors of Pediatric Medulloblastoma
| Autor: | Bhakti Dwivedi, Tricia Z. King, Manali Rupji, Benjamin I Siegel, Jeanne Kowalski, Tobey J. MacDonald, Alexis B. Carter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Medulloblastoma Oncology Original article Cancer Research medicine.medical_specialty business.industry DNA repair Cancer medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Outcome (game theory) Noncoding DNA lcsh:RC254-282 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Text mining 030220 oncology & carcinogenesis Internal medicine medicine business Gene Neurocognitive |
| Zdroj: | Translational Oncology, Vol 12, Iss 7, Pp 908-916 (2019) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | Host genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology, are limited. Here, we evaluated variation in host genome of long-term survivors of medulloblastoma and its association with neurocognitive outcome. Whole-genome sequencing was conducted on peripheral blood of long-term survivors of pediatric medulloblastoma who also completed neuropsychological testing. Cognitively impaired and less impaired survivors did not differ in exposure to chemoradiation therapy or age at treatment. Unsupervised consensus clustering yielded two distinct variant clusters that were significantly associated with neurocognitive outcome. Interestingly, 34 of the 36 significant variants were found in noncoding DNA regions with unknown regulatory function. A separate unsupervised cluster analysis of variants within DNA repair genes identified discrete variant groups that were not associated with neurocognitive outcome, suggesting that variations in genes corresponding to a single functional group may be insufficient to predict long-term outcome alone. These findings are supportive of the presence of a genetic diathesis for treatment-related neurocognitive morbidity in medulloblastoma that may be driven by variation in noncoding regulatory elements. |
| Databáze: | OpenAIRE |
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