PDF(Pubmed)
Abstract：
A 40-year old female patient from the Chinese Han population presented colorectal cancer (CRC) related symptoms including abdominal discomfort, tenesmus and severe back pain, and was admitted to the First Affiliated Anhui Medical University in October, 2008. The size of her tumor was 3 cm × 3 cm, and the carcinoma had invaded the serosa layer, covering 3/4 of the intestine tube. She was diagnosed with stage III CRC after examination. The patient presented a good prognosis with over 8-year survival after curative surgery and adjuvant therapy with Oxaliplatin and Huaier granules, a traditional Chinese medicine. Using the whole-genome sequencing (WGS) data, we profiled the germline and somatic mutations and obtained an all-inclusive data of the genomic alterations. The genomic alterations were compared with those of stage III CRC patients in The Cancer Genome Atlas Network (TCGA). Mutations in APC, TP53, KRAS, SMAD4, FBXW7 and PIK3CA defined as drivers in TCGA patients were not recorded in our study. However, mutations in MUC4, MUC16, ARID1B, BAZ1A, BRCA2, CTNND1 and NCOA2 rarely reported in TCGA patients were predominant in our patient. Additionally, we observed loss of heterozygosity (LOH) in POLE, RET, BMPR1A, NCOA4 and 30 other genes in contrast to deletion and amplification events recorded in TCGA patients. Overall, we produced a genomic mutation profile of a long-term surviving CRC patient and identified recurrent and rare mutations that could provide a valuable resource for further study into the alterations that characterize advanced CRC which may be useful to design clinical therapy for personalized medicine.
摘要：
一名来自中国汉族人群的40岁女性患者出现结直肠癌（CRC）相关症状，包括腹部不适，里急后重和严重的背痛，10月考入安徽医科大学第一附属医学院,2008.她的肿瘤大小为3厘米×3厘米，癌侵入了浆膜层，覆盖3/4的肠管。她在检查后被诊断为III期CRC。经根治性手术及奥沙利铂、淮儿颗粒辅助治疗，预后良好，生存8年以上，一种传统的中药。使用全基因组测序（WGS）数据，我们分析了种系和体细胞突变，并获得了基因组改变的全部数据。在癌症基因组图谱网络（TCGA）中将基因组改变与III期CRC患者进行比较。APC中的突变，TP53,KRAS,在我们的研究中没有记录被定义为TCGA患者的驱动因素的SMAD4、FBXW7和PIK3CA。然而,MUC4，MUC16，ARID1B，BAZ1A,在TCGA患者中很少报道的BRCA2，CTNND1和NCOA2在我们的患者中占主导地位。此外,我们观察到POLE的杂合性丢失（LOH），RET,BMPR1A,与在TCGA患者中记录的缺失和扩增事件相反,NCOA4和30个其他基因。总的来说,我们制作了一个长期存活的CRC患者的基因组突变谱,并鉴定了复发和罕见突变,这些突变可以为进一步研究晚期CRC的特征改变提供有价值的资源,这些改变可能有助于设计个性化药物的临床治疗.
