دورية أكاديمية
Germline genetic regulation of the colorectal tumor immune microenvironment
| العنوان: | Germline genetic regulation of the colorectal tumor immune microenvironment |
|---|---|
| المؤلفون: | Stephanie L. Schmit, Ya-Yu Tsai, Joseph D. Bonner, Rebeca Sanz-Pamplona, Amit D. Joshi, Tomotaka Ugai, Sidney S. Lindsey, Marilena Melas, Kevin J. McDonnell, Gregory E. Idos, Christopher P. Walker, Chenxu Qu, W. Martin Kast, Diane M. Da Silva, Jonathan N. Glickman, Andrew T. Chan, Marios Giannakis, Jonathan A. Nowak, Hedy S. Rennert, Harlan S. Robins, Shuji Ogino, Joel K. Greenson, Victor Moreno, Gad Rennert, Stephen B. Gruber |
| المصدر: | BMC Genomics, Vol 25, Iss 1, Pp 1-14 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biotechnology LCC:Genetics |
| مصطلحات موضوعية: | Genetic polymorphisms, T cell responses, Colorectal Cancer, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| الوصف: | Abstract Objective To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC). Methods Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA). Tumor infiltrating lymphocytes per high powered field (TILs/hpf) were scored by a gastrointestinal pathologist. Regression models were used to evaluate the associations between each variant and the three T-cell features, adjusting for sex, age, genotyping platform, and global ancestry. Three independent datasets were used for replication. Results We identified a SNP (rs4918567) near RBM20 associated with clonality at a genome-wide significant threshold of 5 × 10− 8, with a consistent direction of association in both discovery and replication datasets. Expression quantitative trait (eQTL) analyses and in silico functional annotation for these loci provided insights into potential functional roles, including a statistically significant eQTL between the T allele at rs4918567 and higher expression of ADRA2A (P = 0.012) in healthy colon mucosa. Conclusions Our study suggests that germline genetic variation is associated with the quantity and diversity of adaptive immune responses in CRC. Further studies are warranted to replicate these findings in additional samples and to investigate functional genomic mechanisms. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2164 |
| العلاقة: | https://doaj.org/toc/1471-2164Test |
| DOI: | 10.1186/s12864-024-10295-1 |
| الوصول الحر: | https://doaj.org/article/bfa9ed09e404405395677a797686e21cTest |
| رقم الانضمام: | edsdoj.bfa9ed09e404405395677a797686e21c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14712164 |
|---|---|
| DOI: | 10.1186/s12864-024-10295-1 |