title: Whole-exome sequencing predicted cancer epitope trees of 23 early cervical cancers in Chinese women.
abstract: Emerging evidence suggest that the heterogeneity of cancer limits the efficacy of immunotherapy. To search for optimal therapeutic targets for enhancing the efficacy, we used whole-exome sequencing data of 23 early cervical tumors from Chinese women to investigate the hierarchical structure of the somatic mutations and the neo-epitopes. The putative neo-epitopes were predicted based on the mutant peptides' strong binding with major histocompatibility complex class I molecules. We found that each tumor carried an average of 117 mutations and 61 putative neo-epitopes. Each patient displayed a unique phylogenetic tree in which almost all subclones harbored neo-epitopes, highlighting the importance of individual neo-epitope tree in determination of immunotherapeutic targets. The alterations in FBXW7 and PIK3CA, or other members of the significantly altered ubiquitin-mediated proteolysis and extracellular matrix receptor interaction related pathways, were proposed as the earliest changes triggering the malignant progression. The neo-epitopes involved in these pathways, and located at the top of the hierarchy tree, might become the optimal candidates for therapeutic targets, possessing the potential to mediate T-cell killing of the descendant cells. These findings expanded our understanding in early stage of cervical carcinogenesis and offered an important approach to assist optimizing the immunotherapeutic target selection.
authors.affiliation: The Laboratory for Gene and Cell Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.|Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Geneplus-Beijing, Beijing, 102206, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Geneplus-Beijing, Beijing, 102206, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Gong
authors.affiliation: The Laboratory for Gene and Cell Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: He
authors.affiliation: Geneplus-Beijing, Beijing, 102206, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|School of Basic Medical Sciences, Center for Genetic and Genomic Medicine, Zhejiang University Medical School 1st Affiliated Hospital James Watson Institute of Genome Sciences, Hangzhou, Zhejiang, China.|Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.affiliation: The Laboratory for Gene and Cell Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D055088:Early Detection of Cancer; D000939:Epitopes / Q000378:metabolism*; D059472:Exome; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D009154:Mutation; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology*; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000821:virology
chemical_list: D018797:Cell Cycle Proteins; D000939:Epitopes; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Cervical cancer; immunotherapeutic target; neo-epitope; phylogenetic tree