马来族结直肠癌患者完整错配修复蛋白的全基因组图谱。
Whole-Genome Profiles of Malay Colorectal Cancer Patients with Intact MMR Proteins.
机构信息
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.
Malaysian Node of the Human Variome Project, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.
出版信息
Genes (Basel). 2021 Sep 20;12(9):1448. doi: 10.3390/genes12091448.
BACKGROUND
This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.
METHOD
Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.
RESULTS
An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes- and -which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes- and -harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.
CONCLUSION
This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.
背景
本研究旨在鉴定在错配修复（MMR）蛋白表达正常的 CRC 患者中与 CRC 相关的新基因。
方法
对 7 名早发马来 CRC 患者进行全基因组测序（WGS）。使用功能和预测算法对潜在的种系遗传变异，包括单核苷酸变异和插入缺失（indels）进行优先排序。
结果
鉴定出平均 320 万个单核苷酸变异（SNVs）和 800 多个插入缺失。在 3 名马来 CRC 患者中鉴定出三个基因-和 -中的三个潜在候选变异，这些变异被预测会影响蛋白质功能。此外，优先考虑了 19 个候选基因-和 -，它们含有无义变异。这些基因被认为在癌症易感性中起作用，并与癌症风险相关。通路富集分析表明嗅觉信号通路显著富集。
结论
本研究为马来患者 CRC 相关的潜在基因、变异和通路提供了新的见解。
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