التفاصيل البيبلوغرافية
| العنوان: |
Mutational Signatures Driven by Epigenetic Determinants Enable the Stratification of Patients with Gastric Cancer for Therapeutic Intervention |
| المؤلفون: |
Jaqueline Ramalho Buttura, Monize Nakamoto Provisor Santos, Renan Valieris, Rodrigo Duarte Drummond, Alexandre Defelicibus, João Paulo Lima, Vinicius Fernando Calsavara, Helano Carioca Freitas, Vladmir C. Cordeiro de Lima, Thais Fernanda Bartelli, Marc Wiedner, Rafael Rosales, Kenneth John Gollob, Joanna Loizou, Emmanuel Dias-Neto, Diana Noronha Nunes, Israel Tojal da Silva |
| المصدر: |
Cancers; Volume 13; Issue 3; Pages: 490 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
mutational signature, gastric cancer, DNA mismatch repair, prognosis |
| الوصف: |
DNA mismatch repair deficiency (dMMR) is associated with the microsatellite instability (MSI) phenotype and leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Various mutational signatures directly linked to dMMR have been described for primary cancers. To investigate which mutational signatures are associated with prognosis in gastric cancer, we performed a de novo extraction of mutational signatures in a cohort of 787 patients. We detected three dMMR-related signatures, one of which clearly discriminates tumors with MLH1 gene silencing caused by promoter hypermethylation (area under the curve = 98%). We then demonstrated that samples with the highest exposure of this signature share features related to better prognosis, encompassing clinical and molecular aspects and altered immune infiltrate composition. Overall, the assessment of the prognostic value and of the impact of modifications in MMR-related genes on shaping specific dMMR mutational signatures provides evidence that classification based on mutational signature exposure enables prognosis stratification. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Cancer Causes, Screening and Diagnosis; https://dx.doi.org/10.3390/cancers13030490 |
| DOI: |
10.3390/cancers13030490 |
| الاتاحة: |
https://doi.org/10.3390/cancers13030490 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.AEEC2382 |
| قاعدة البيانات: |
BASE |