Characterization and validation of somatic mutation spectrum to reveal heterogeneity in gastric cancer by single cell sequencing

Gastric cancer(GC) is a highly heterogeneous disease with multiple cellular types and poor prognosis.However, the cellular evolution and molecular basis of GC at the individual intra-tumor level has not been well demonstrated. We performed single-cell whole exome sequencing to detect somatic singlenucleotide variants(SNVs) and significantly mutated genes(SMGs) among 34 tumor cells and 9 normal cells from a patient with GC. The Complete Prediction for Protein Conformation(CPPC) approach directly predicting the folding conformation of the protein 3D structure with Protein Folding Shape Code, combined with functional experiments were used to confirm the characterization of mutated SMGs in GC cells. We identified 201 somatic SNVs, including 117 non-synonymous mutations in GC cells. Further analysis identified 24 significant mutated genes(SMGs) in single cells, for which a single amino acid change might affect protein conformation. Among them, two genes(CDC27 and FLG) that were mutated only in single cells but not in the corresponding tumor tissue, were recurrently present in another GC tissue cohort, and may play a potential role to promote carcinogenesis, as confirmed by functional characterization. Our findings showed a mutational landscape of GC at intra-tumor level for the first time and provided opportunities for understanding the heterogeneity and individualized target therapy for this disease.

高危型人乳头瘤病毒检测对细胞学结果为意义不明的非典型鳞状细胞和低度鳞状上皮内病变的管理价值

目的探讨第二代杂交捕获试验（He一2）检测高危型人乳头瘤病毒（HR．HPV）DNA对细胞学结果为意义不明的非典型鳞状细胞（ASCUS）和低度鳞状上皮内病变（IJsIL）的管理价值。方法收集细胞学结果为ASCUS（178例）和LSIL（108例）的HR-HPV感染情况，以敏感度、特异度、阳性预测值和阴性预测值来评价He-2检测HR-HPVDNA在宫颈病变筛查中的价值。结果He-2检测HR-HPVDNA对于ASCUS中病理结果为宫颈上皮内瘤变（CIN）Ⅱ及其以上级别病变的敏感度为89．83％（53／59），特异度为53．78％（64／119），阳性预测值为49．07％（53／108），阴性预测值为91．43％（64／70）；对于LSIL中CINII及其以上级别病变的敏感度为97．62％（41／42），特异度为22．73％（15／66），阳性预测值为44．57％（41／92），阴性预测值为93．75％（15／16）。结论HR．HPVDNA检测是一种管理细胞学结果为ASCUS和LSIL病例的有效手段。