CancerTracer: a Curated Database for Intrapatient Tumor Heterogeneity

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2019 Nov 9

PMID 31701131

Citations 8

Authors

Chen Wang

Jian Yang

Hong Luo

Kun Wang

Yu Wang

Zhi-Xiong Xiao

Xiang Tao

Hao Jiang

Haoyang Cai

Affiliations

Soon will be listed here.

Abstract

Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. Here, we present a database we've named CancerTracer (http://cailab.labshare.cn/cancertracer): a manually curated database designed to track and characterize the evolutionary trajectories of tumor growth in individual patients. We collected over 6000 tumor samples from 1548 patients corresponding to 45 different types of cancer. Patient-specific tumor phylogenetic trees were constructed based on somatic mutations or copy number alterations identified in multiple biopsies. Using the structured heterogeneity data, researchers can identify common driver events shared by all tumor regions, and the heterogeneous somatic events present in different regions of a tumor of interest. The database can also be used to investigate the phylogenetic relationships between primary and metastatic tumors. It is our hope that CancerTracer will significantly improve our understanding of the evolutionary histories of tumors, and may facilitate the identification of predictive biomarkers for personalized cancer therapies.

Citing Articles

Economic Evaluations of Imaging Biomarker-Driven Companion Diagnostics for Cancer: A Systematic Review.

Liu S, Tan D, Graves N, Chacko A Appl Health Econ Health Policy. 2023; 21(6):841-855.

PMID: 37747620 DOI: 10.1007/s40258-023-00833-5.

Engineering Cancer/Testis Antigens With Reversible Cationization to Evaluate Antigen Spreading.

Miyamoto A, Honjo T, Masui M, Kinoshita R, Kumon H, Kakimi K Front Oncol. 2022; 12:869393.

PMID: 35600379 PMC: 9115381. DOI: 10.3389/fonc.2022.869393.

Coordination games in cancer.

Bayer P, Gatenby R, McDonald P, Duckett D, Stankova K, Brown J PLoS One. 2022; 17(1):e0261578.

PMID: 35061724 PMC: 8782377. DOI: 10.1371/journal.pone.0261578.

A zinc finger protein gene signature enables bladder cancer treatment stratification.

Zhang J, Zhang C, Cao P, Zheng X, Yu B, Cao H Aging (Albany NY). 2021; 13(9):13023-13038.

PMID: 33962398 PMC: 8148496. DOI: 10.18632/aging.202984.

High Throughput Multi-Omics Approaches for Clinical Trial Evaluation and Drug Discovery.

Zielinski J, Luke J, Guglietta S, Krieg C Front Immunol. 2021; 12:590742.

PMID: 33868223 PMC: 8044891. DOI: 10.3389/fimmu.2021.590742.

References

Ghandi M, Huang F, Jane-Valbuena J, Kryukov G, Lo C, McDonald 3rd E . Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019; 569(7757):503-508. PMC: 6697103. DOI: 10.1038/s41586-019-1186-3. View

Kwak E, Ahronian L, Siravegna G, Mussolin B, Borger D, Godfrey J . Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer. Cancer Discov. 2015; 5(12):1271-81. PMC: 4670804. DOI: 10.1158/2159-8290.CD-15-0748. View

Tate J, Bamford S, Jubb H, Sondka Z, Beare D, Bindal N . COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2018; 47(D1):D941-D947. PMC: 6323903. DOI: 10.1093/nar/gky1015. View

Murugaesu N, Wilson G, Birkbak N, Watkins T, McGranahan N, Kumar S . Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy. Cancer Discov. 2015; 5(8):821-831. PMC: 4529488. DOI: 10.1158/2159-8290.CD-15-0412. View

Lawrence M, Stojanov P, Mermel C, Robinson J, Garraway L, Golub T . Discovery and saturation analysis of cancer genes across 21 tumour types. Nature. 2014; 505(7484):495-501. PMC: 4048962. DOI: 10.1038/nature12912. View

Dagogo-Jack I, Shaw A . Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2017; 15(2):81-94. DOI: 10.1038/nrclinonc.2017.166. View

Hao J, Lin D, Dinh H, Mayakonda A, Jiang Y, Chang C . Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma. Nat Genet. 2016; 48(12):1500-1507. PMC: 5127772. DOI: 10.1038/ng.3683. View

Rogers M, Shihab H, Mort M, Cooper D, Gaunt T, Campbell C . FATHMM-XF: accurate prediction of pathogenic point mutations via extended features. Bioinformatics. 2017; 34(3):511-513. PMC: 5860356. DOI: 10.1093/bioinformatics/btx536. View

Alexandrov L, Nik-Zainal S, Wedge D, Aparicio S, Behjati S, Biankin A . Signatures of mutational processes in human cancer. Nature. 2013; 500(7463):415-21. PMC: 3776390. DOI: 10.1038/nature12477. View

10.

Zhang H, Luo S, Zhang X, Liao J, Quan F, Zhao E . SEECancer: a resource for somatic events in evolution of cancer genome. Nucleic Acids Res. 2017; 46(D1):D1018-D1026. PMC: 5753201. DOI: 10.1093/nar/gkx964. View

11.

Yates L, Campbell P . Evolution of the cancer genome. Nat Rev Genet. 2012; 13(11):795-806. PMC: 3666082. DOI: 10.1038/nrg3317. View

12.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

13.

Bailey M, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A . Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell. 2018; 173(2):371-385.e18. PMC: 6029450. DOI: 10.1016/j.cell.2018.02.060. View

14.

Jamal-Hanjani M, Wilson G, McGranahan N, Birkbak N, Watkins T, Veeriah S . Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 376(22):2109-2121. DOI: 10.1056/NEJMoa1616288. View

15.

Chen X, Zhong Q, Liu Y, Yan S, Chen Z, Jin S . Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing. Nat Commun. 2017; 8(1):524. PMC: 5595870. DOI: 10.1038/s41467-017-00650-0. View

16.

Shi W, Ng C, Lim R, Jiang T, Kumar S, Li X . Reliability of Whole-Exome Sequencing for Assessing Intratumor Genetic Heterogeneity. Cell Rep. 2018; 25(6):1446-1457. PMC: 6261536. DOI: 10.1016/j.celrep.2018.10.046. View

17.

Zhang J, Fujimoto J, Zhang J, Wedge D, Song X, Zhang J . Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014; 346(6206):256-9. PMC: 4354858. DOI: 10.1126/science.1256930. View

18.

Gerlinger M, McGranahan N, Dewhurst S, Burrell R, Tomlinson I, Swanton C . Cancer: evolution within a lifetime. Annu Rev Genet. 2014; 48:215-36. DOI: 10.1146/annurev-genet-120213-092314. View

19.

Russo M, Siravegna G, Blaszkowsky L, Corti G, Crisafulli G, Ahronian L . Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer. Cancer Discov. 2015; 6(2):147-153. PMC: 4744519. DOI: 10.1158/2159-8290.CD-15-1283. View

20.

Zhai W, Kiat-Hon Lim T, Zhang T, Phang S, Tiang Z, Guan P . The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma. Nat Commun. 2017; 8:4565. PMC: 5333358. DOI: 10.1038/ncomms14565. View