Multiple region whole-exome sequencing reveals dramatically evolving intratumor genomic heterogeneity in esophageal squamous cell carcinoma

生物 外显子组测序 遗传异质性 癌症的体细胞进化 比较基因组杂交 外显子组 遗传学 非同义代换 桑格测序 拷贝数变化 基因组学 癌症 计算生物学 基因 突变 基因组 表型
作者
Wei Cao,Wei Wu,Ming Yan,Fei Tian,Chi Ma,Q Zhang,X Li,Peng Han,Z Liu,Jianying Gu,Fred G. Biddle
出处
期刊:Oncogenesis [Springer Nature]
卷期号:4 (11): e175-e175 被引量:51
标识
DOI:10.1038/oncsis.2015.34
摘要

Cancer is a disease of genome instability and genomic alterations; now, genomic heterogeneity is rapidly emerging as a defining feature of cancer, both within and between tumors. Motivation for our pilot study of tumor heterogeneity in esophageal squamous cell carcinoma (ESCC) is that it is not well studied, but the highest incidences of esophageal cancers are found in China and ESCC is the most common type. We profiled the mutations and changes in copy number that were identified by whole-exome sequencing and array-based comparative genomic hybridization in multiple regions within an ESCC from two patients. The average mutational heterogeneity rate was 90% in all regions of the individual tumors in each patient; most somatic point mutations were nonsynonymous substitutions, small Indels occurred in untranslated regions of genes, and copy number alterations varied among multiple regions of a tumor. Independent Sanger sequencing technology confirmed selected gene mutations with more than 88% concordance. Phylogenetic analysis of the somatic mutation frequency demonstrated that multiple, genomically heterogeneous divergent clones evolve and co-exist within a primary ESCC and metastatic subclones result from the dispersal and adaptation of an initially non-metastatic parental clone. Therefore, a single-region sampling will not reflect the evolving architecture of a genomically heterogeneous landscape of mutations in ESCC tumors and the divergent complexity of this genomic heterogeneity among patients will complicate any promise of a simple genetic or epigenetic diagnostic signature in ESCC. We conclude that any potential for informative biomarker discovery in ESCC and targeted personalized therapies will require a deeper understanding of the functional biology of the ontogeny and phylogeny of the tumor heterogeneity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
研友_8yN60L发布了新的文献求助10
刚刚
Xi完成签到,获得积分10
3秒前
大方的天空完成签到,获得积分10
3秒前
妍宝贝发布了新的文献求助20
3秒前
5秒前
6秒前
Mannose发布了新的文献求助20
6秒前
6秒前
Lyn应助舍予舍予采纳,获得10
6秒前
欢呼水蜜桃完成签到,获得积分10
6秒前
7秒前
袁yuan完成签到,获得积分10
7秒前
8秒前
8秒前
9秒前
9秒前
9秒前
coco发布了新的文献求助10
10秒前
852应助调皮竺采纳,获得10
10秒前
10秒前
mmyhn发布了新的文献求助10
11秒前
11秒前
顺利毕业发布了新的文献求助20
11秒前
asdfj发布了新的文献求助10
12秒前
苗苗子子发布了新的文献求助10
12秒前
你好啊发布了新的文献求助50
13秒前
CodeCraft应助个性的冬卉采纳,获得10
13秒前
13秒前
年轻绮露发布了新的文献求助20
13秒前
小蘑菇应助ylf采纳,获得10
14秒前
Singularity发布了新的文献求助10
14秒前
15秒前
15秒前
1+1发布了新的文献求助10
15秒前
16秒前
廿秦完成签到,获得积分10
16秒前
执着忆枫完成签到,获得积分10
17秒前
17秒前
xxyy发布了新的文献求助10
19秒前
19秒前
高分求助中
歯科矯正学 第7版(或第5版) 1004
The late Devonian Standard Conodont Zonation 1000
Semiconductor Process Reliability in Practice 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 700
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 600
Zeitschrift für Orient-Archäologie 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3237112
求助须知:如何正确求助?哪些是违规求助? 2882693
关于积分的说明 8227913
捐赠科研通 2550880
什么是DOI,文献DOI怎么找? 1379511
科研通“疑难数据库(出版商)”最低求助积分说明 648708
邀请新用户注册赠送积分活动 624275