Academic Journal
Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer
| العنوان: | Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer |
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| المؤلفون: | Xie, Zhengyong, Ke, Yongli, Chen, Junyong, Li, Zehang, Wang, Changzheng, Chen, Yuhong, Ding, Hongliang, Cheng, Liyang |
| المصدر: | Frontiers in Genetics ; volume 12 ; ISSN 1664-8021 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2022 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Background: Bowel cancer is the third-most common cancer and the second leading cause of cancer-related death worldwide. Bowel cancer has a substantial hereditary component; however, additional hereditary risk factors involved in bowel cancer pathogenesis have not been systematically defined. Materials and Methods: A total of 573 patients with bowel cancer were enrolled in the present study, of whom 93.72% had colorectal cancer (CRC). Germline mutations were integrated with somatic mutation information via utilizing target next-generation sequencing. Results: Pathogenic/Likely Pathogenic (P/LP) germline alterations were identified in 47 (8.2%) patients with bowel cancer and the ratio of the number of these patients with family history was significantly higher in the P/LP group than that noted in the non-pathogenic (Non-P) group. Certain rare germline alterations were noted, such as those noted in the following genes: FANCD2, CDH1 , and FLCN . A total of 32 patients (68.1%) had germline alterations in the DNA-damage repair (DDR) genes and homologous recombination (HR) accounted for the highest proportion of this subgroup. By comparing 573 patients with bowel cancer with reference controls (China_MAPs database), significant associations ( p < 0.01) were observed between the incidence of bowel cancer and the presence of mutations in APC, ATM, MLH1, FANCD2, MSH3, MSH6, PMS1 , and RAD51D . Somatic gene differential analysis revealed a marked difference in 18 genes and a significant difference was also noted in tumor mutation burden (TMB) between germline mutation carriers and non-germline mutation subjects ( p < 0.001). In addition, TMB in DDR mutation groups indicated a dramatic difference compared with the non-DDR mutation group ( p < 0.01). However, no statistically significant differences in TMB were noted among detailed DDR pathways for patients with bowel cancer, irrespective of the presence of germline mutations. Moreover, a significantly higher level ( p < 0.0001) of mutation count ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fgene.2021.755629 |
| DOI: | 10.3389/fgene.2021.755629/full |
| الاتاحة: | http://dx.doi.org/10.3389/fgene.2021.755629 https://www.frontiersin.org/articles/10.3389/fgene.2021.755629/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.90F695E0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fgene.2021.755629 |
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