Reynolds Ian S, Thomas Valentina, O'Connell Emer, Fichtner Michael, McNamara Deborah A, Kay Elaine W, Prehn Jochen H M, Burke John P, Furney Simon J
Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland.
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Front Oncol. 2020 Aug 26;10:1682. doi: 10.3389/fonc.2020.01682. eCollection 2020.
Mucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this study was to comprehensively describe the burden of somatic mutations and copy number variation as well as perform mutational signature and microbial analysis of an in-house collected cohort of mucinous adenocarcinoma of the rectum.
Genomic DNA was extracted from 10 cases of mucinous rectal cancer and matched normal tissue. Whole genome sequencing (WGS) was carried out on these 10 cases and a comprehensive bioinformatic analysis was undertaken.
The average number of SNVs, InDels and SVs in the cohort was 16,600, 1,855, and 120, respectively. A single case was MSI-H. mutations were found in 70% of cases while was mutated in only 40% of cases. CNA gain was identified on chromosomes 7, 8, 12, 13, and 20 while CNA loss was found on chromosomes 4, 8, 17, and 18 corresponding to oncogenes and tumor suppressor genes, respectively. Overall mucinous rectal cancers are more likely to be MSI-H and to have , , and mutations when compared to rectal adenocarcinoma NOS. Microbial analysis demonstrated an abundance of in tumor samples compared to normal tissue.
This study provides a detailed WGS analysis of 10 cases of mucinous rectal cancer. It demonstrates an important lesson in tumor biology in that histologically similar tumors can have extensive differences at the genomic level. This study is relevant as it raises important questions about the relationship between bacteria and malignancy.
直肠黏液腺癌是一种罕见的组织学亚型，与放化疗反应受损及总体预后较差相关。目前尚未对直肠黏液性肿瘤进行基因组图谱分析。本研究的目的是全面描述体细胞突变和拷贝数变异的负担，并对内部收集的直肠黏液腺癌队列进行突变特征和微生物分析。
从10例直肠黏液癌及配对的正常组织中提取基因组DNA。对这10例样本进行全基因组测序（WGS）并开展全面的生物信息学分析。
该队列中，单核苷酸变异（SNV）、插入缺失（InDel）和结构变异（SV）的平均数量分别为16,600、1,855和120。1例为微卫星高度不稳定（MSI-H）。70%的病例中发现 突变，而只有40%的病例中 发生突变。在7号、8号、12号、13号和20号染色体上发现拷贝数增加（CNA增益），而在4号、8号、17号和18号染色体上发现CNA缺失，分别对应癌基因和肿瘤抑制基因。总体而言，与非特殊类型直肠腺癌相比，直肠黏液癌更可能为MSI-H，且具有 、 和 突变。微生物分析表明，与正常组织相比，肿瘤样本中 含量丰富。
本研究对10例直肠黏液癌进行了详细的WGS分析。它在肿瘤生物学方面提供了重要经验，即组织学相似的肿瘤在基因组水平可能存在广泛差异。本研究具有相关性，因为它提出了关于细菌与恶性肿瘤之间关系的重要问题。
