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两种不同规模的基于扩增子测序的检测板在检测与胃癌相关的体细胞突变中的比较。

Comparison between two amplicon-based sequencing panels of different scales in the detection of somatic mutations associated with gastric cancer.

作者信息

Hirotsu Yosuke, Kojima Yuichiro, Okimoto Kenichiro, Amemiya Kenji, Mochizuki Hitoshi, Omata Masao

机构信息

Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan.

Department of Gastroenterology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, 400-8506, Japan.

出版信息

BMC Genomics. 2016 Oct 26;17(1):833. doi: 10.1186/s12864-016-3166-4.

Abstract

BACKGROUND

Sequencing data from The Cancer Genome Atlas (TGCA), the International Cancer Genome Consortium and other research institutes have revealed the presence of genetic alterations in several tumor types, including gastric cancer. These data have been combined into a catalog of significantly mutated genes for each cancer type. However, it is unclear to what extent significantly mutated genes need to be examined for detecting genetic alterations in gastric cancer patients. Here, we constructed two custom-made sequencing panels of different scales, the Selective hotspot Panel and the Comprehensive Panel, to analyze genetic alterations in 21 resected specimens endoscopically obtained from 20 gastric cancer patients, and we assessed how many mutations were detectable using these different panels.

RESULTS

A total of 21 somatic mutations were identified by the Selective hotspot Panel and 70 mutations were detected by the Comprehensive Panel. All mutations identified by the Selective hotspot Panel were detected by the Comprehensive Panel, with high concordant values of the variant allelic fraction of each mutation (correlation coefficient, R = 0.92). At least one mutation was identified in 13 patients (65 %) by the Selective hotspot Panel, whereas the Comprehensive Panel detected mutations in 19 (95 %) patients. Library preparation and sequencing costs were comparable between the two panels.

CONCLUSIONS

Our results indicate the utility of comprehensive panel-based targeted sequencing in gastric cancer.

摘要

背景

来自癌症基因组图谱(TGCA)、国际癌症基因组联盟及其他研究机构的测序数据已揭示了包括胃癌在内的多种肿瘤类型中存在基因改变。这些数据已被整合为每种癌症类型的显著突变基因目录。然而,对于检测胃癌患者的基因改变而言,需要检测显著突变基因到何种程度尚不清楚。在此,我们构建了两个不同规模的定制测序面板,即选择性热点面板和综合面板,以分析从20例胃癌患者内镜获取的21份切除标本中的基因改变,并且我们评估了使用这些不同面板可检测到多少突变。

结果

选择性热点面板共鉴定出21个体细胞突变,综合面板检测到70个突变。选择性热点面板鉴定出的所有突变均被综合面板检测到,每个突变的变异等位基因分数具有高度一致性值(相关系数,R = 0.92)。选择性热点面板在13例患者(65%)中鉴定出至少一个突变,而综合面板在19例(95%)患者中检测到突变。两个面板之间文库制备和测序成本相当。

结论

我们的结果表明基于综合面板的靶向测序在胃癌中的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ac/5080794/6ac927952809/12864_2016_3166_Fig1_HTML.jpg

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