Identification of Copy Number Alterations in Colon Cancer from Analysis of Amplicon-based Next Generation Sequencing Data

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 May 15

PMID 29755661

Citations 11

Authors

Duarte Mendes Oliveira

Gianluca Santamaria

Carmelo Laudanna

Simona Migliozzi

Pietro Zoppoli

Michael Quist

Catie Grasso

Chiara Mignogna

Laura Elia

Maria Concetta Faniello

Cinzia Marinaro

Rosario Sacco

Francesco Corcione

Giuseppe Viglietto

Donatella Malanga

Antonia Rizzuto

Affiliations

Soon will be listed here.

Abstract

The objective of this study was to determine the feasibility to detect copy number alterations in colon cancer samples using Next Generation Sequencing data and to elucidate the association between copy number alterations in specific genes and the development of cancer in different colon segments. We report the successful detection of somatic changes in gene copy number in 37 colon cancer patients by analysis of sequencing data through Amplicon CNA Algorithm. Overall, we have found a total of 748 significant copy number alterations in 230 significant genes, of which 143 showed CN losses and 87 showed CN gains. Validation of results was performed on 20 representative genes by quantitative qPCR and/or immunostaining. By this analysis, we have identified 4 genes that were subjected to copy number alterations in tumors arising in all colon segments (defined "common genes") and the presence of copy number alterations in 14 genes that were significantly associated to one specific site (defined "site-associated genes"). Finally, copy number alterations in ASXL1, TSC1 and IL7R turned out to be clinically relevant since the loss of TSC1 and IL7R was associated with advanced stages and/or reduced survival whereas copy number gain of ASXL1 was associated with good prognosis.

Citing Articles

Identification of novel diagnostic biomarkers associated with liver metastasis in colon adenocarcinoma by machine learning.

Yang L, Tian Y, Cao X, Wang J, Luo B Discov Oncol. 2024; 15(1):542.

PMID: 39390264 PMC: 11467158. DOI: 10.1007/s12672-024-01398-y.

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.

Carey-Smith S, Kotecha R, Cheung L, Malinge S Int J Mol Sci. 2024; 25(13).

PMID: 38999925 PMC: 11241182. DOI: 10.3390/ijms25136815.

Multi-omics prognostic signatures of IPO11 mRNA expression and clinical outcomes in colorectal cancer using bioinformatics approaches.

Aljahdali M, Molla M Health Inf Sci Syst. 2023; 11(1):57.

PMID: 38028961 PMC: 10678892. DOI: 10.1007/s13755-023-00259-2.

Construction and validation of a prognostic model for gastrointestinal stromal tumors based on copy number alterations and clinicopathological characteristics.

Zhao H, Song N, Feng H, Lei Q, Zheng Y, Liu J Front Oncol. 2023; 12:1055174.

PMID: 36620561 PMC: 9811389. DOI: 10.3389/fonc.2022.1055174.

Colorectal cancer concurrent gene signature based on coherent patterns between genomic and transcriptional alterations.

Shen M, Huang C, Ho T, Liu C, Shih Y, Huang C BMC Cancer. 2022; 22(1):590.

PMID: 35637462 PMC: 9150289. DOI: 10.1186/s12885-022-09627-9.

References

McCarroll S, Kuruvilla F, Korn J, Cawley S, Nemesh J, Wysoker A . Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet. 2008; 40(10):1166-74. DOI: 10.1038/ng.238. View

Venkatachalam R, Ligtenberg M, Hoogerbrugge N, Geurts van Kessel A, Kuiper R . Predisposition to colorectal cancer: exploiting copy number variation to identify novel predisposing genes and mechanisms. Cytogenet Genome Res. 2009; 123(1-4):188-94. DOI: 10.1159/000184708. View

Ashktorab H, Schaffer A, Daremipouran M, Smoot D, Lee E, Brim H . Distinct genetic alterations in colorectal cancer. PLoS One. 2010; 5(1):e8879. PMC: 2811180. DOI: 10.1371/journal.pone.0008879. View

Behjati S, Tarpey P, Sheldon H, Martincorena I, Van Loo P, Gundem G . Recurrent PTPRB and PLCG1 mutations in angiosarcoma. Nat Genet. 2014; 46(4):376-379. PMC: 4032873. DOI: 10.1038/ng.2921. View

Nakao K, Mehta K, Fridlyand J, Moore D, Jain A, Lafuente A . High-resolution analysis of DNA copy number alterations in colorectal cancer by array-based comparative genomic hybridization. Carcinogenesis. 2004; 25(8):1345-57. DOI: 10.1093/carcin/bgh134. View

Diep C, Kleivi K, Ribeiro F, Teixeira M, Lindgjaerde O, Lothe R . The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer. 2005; 45(1):31-41. DOI: 10.1002/gcc.20261. View

Weir B, Woo M, Getz G, Perner S, Ding L, Beroukhim R . Characterizing the cancer genome in lung adenocarcinoma. Nature. 2007; 450(7171):893-8. PMC: 2538683. DOI: 10.1038/nature06358. View

Ji H, Kumm J, Zhang M, Farnam K, Salari K, Faham M . Molecular inversion probe analysis of gene copy alterations reveals distinct categories of colorectal carcinoma. Cancer Res. 2006; 66(16):7910-9. PMC: 2943417. DOI: 10.1158/0008-5472.CAN-06-0595. View

Baudis M . Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data. BMC Cancer. 2007; 7:226. PMC: 2225423. DOI: 10.1186/1471-2407-7-226. View

10.

Sayagues J, Fontanillo C, Abad M, Gonzalez-Gonzalez M, Sarasquete M, Chillon M . Mapping of genetic abnormalities of primary tumours from metastatic CRC by high-resolution SNP arrays. PLoS One. 2010; 5(10):e13752. PMC: 2966422. DOI: 10.1371/journal.pone.0013752. View

11.

Futreal P, Coin L, Marshall M, Down T, Hubbard T, Wooster R . A census of human cancer genes. Nat Rev Cancer. 2004; 4(3):177-83. PMC: 2665285. DOI: 10.1038/nrc1299. View

12.

Brosens R, Haan J, Carvalho B, Rustenburg F, Grabsch H, Quirke P . Candidate driver genes in focal chromosomal aberrations of stage II colon cancer. J Pathol. 2010; 221(4):411-24. DOI: 10.1002/path.2724. View

13.

Stephens P, McBride D, Lin M, Varela I, Pleasance E, Simpson J . Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature. 2009; 462(7276):1005-10. PMC: 3398135. DOI: 10.1038/nature08645. View

14.

Lin Y, Yang Z, Xu A, Dong P, Huang Y, Liu H . PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway. Sci Rep. 2015; 5:8997. PMC: 4355729. DOI: 10.1038/srep08997. View

15.

Chu D, Zhang Z, Zhou Y, Wang W, Li Y, Zhang H . Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer. Ann Oncol. 2011; 22(11):2440-2447. DOI: 10.1093/annonc/mdq776. View

16.

Lonigro R, Grasso C, Robinson D, Jing X, Wu Y, Cao X . Detection of somatic copy number alterations in cancer using targeted exome capture sequencing. Neoplasia. 2011; 13(11):1019-25. PMC: 3223606. DOI: 10.1593/neo.111252. View

17.

Lin C, Lin J, Chang S, Chang Y, Chang H, Liu J . Molecular profile and copy number analysis of sporadic colorectal cancer in Taiwan. J Biomed Sci. 2011; 18:36. PMC: 3123622. DOI: 10.1186/1423-0127-18-36. View

18.

Poulogiannis G, Ichimura K, Hamoudi R, Luo F, Leung S, Yuen S . Prognostic relevance of DNA copy number changes in colorectal cancer. J Pathol. 2009; 220(3):338-47. DOI: 10.1002/path.2640. View

19.

Stuart D, Sellers W . Linking somatic genetic alterations in cancer to therapeutics. Curr Opin Cell Biol. 2009; 21(2):304-10. DOI: 10.1016/j.ceb.2009.02.001. View

20.

Kim T, Xi R, Luquette L, Park R, Johnson M, Park P . Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 2012; 23(2):217-27. PMC: 3561863. DOI: 10.1101/gr.140301.112. View