Skip to main content
SpringerLink
Log in

Comparison of genetic variation between primary colorectal cancer and metastatic peritoneal cancer

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

Background

Among cancer metastases by primary colorectal cancer (CRC), peritoneal metastasis is the second most common metastatic lesion after liver metastasis. In treating metastatic CRC, it is very important to differentiate targeted-therapy and chemotherapy according to the characteristics of each lesion because the genetic variation of the primary and metastatic lesions are different. However, there are few studies of genetic characteristics on peritoneal metastasis caused by primary CRC, so molecular-level studies are continuously required.

Objective

We propose an appropriate peritoneal metastasis treatment policy by identifying the genetic characteristics between primary CRC and synchronous peritoneal metastatic lesions.

Methods

Primary CRC and synchronous peritoneal metastasis samples were analyzed in pairs from six patients using Comprehensive Cancer Panel (409 cancer-related genes, Thermo Fisher Scientific, USA) and next-generation sequencing (NGS).

Results

The mutations were commonly found on the KMT2C and THBS1 genes in both primary CRC and peritoneal metastasis. The PDE4DIP gene was mutated in all cases except for on a sample of peritoneal metastasis. As a result of analysis using the mutation database, we confirmed that the gene mutations of primary CRC and the peritoneal metastasis derived from it showed the same tendency, although we did not accompany the gene expression level or epigenetic study.

Conclusion

It is thought that the treatment policy through molecular genetic testing of primary CRC can also be applied to peritoneal metastasis treatment. Our study is expected to be the basis for further peritoneal metastasis research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The raw data in this study are available upon reasonable request.

References

  • Aoyagi T, Terracina KP, Raza A, Takabe K (2014) Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol 20:12493–12500

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bertucci F, Finetti P, Guille A, Adelaide J, Garnier S, Carbuccia N, Monneur A, Charafe-Jauffret E, Goncalves A, Viens P et al (2016) Comparative genomic analysis of primary tumors and metastases in breast cancer. Oncotarget 7:27208–27219

    PubMed  PubMed Central  Google Scholar 

  • Brannon AR, Vakiani E, Sylvester BE, Scott SN, McDermott G, Shah RH, Kania K, Viale A, Oschwald DM, Vacic V et al (2014) Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol 15:454

    PubMed  PubMed Central  Google Scholar 

  • Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331:1559–1564

    CAS  PubMed  Google Scholar 

  • Cho YS, Kim H, Kim HM, Jho S, Jun J, Lee YJ, Chae KS, Kim CG, Kim S, Eriksson A et al (2016) An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes. Nat Commun 7:13637

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dahlmann M, Gambara G, Brzezicha B, Popp O, Pachmayr E, Wedeken L, Pflaume A, Mokritzkij M, Gul-Klein S, Brandl A et al (2021) Peritoneal metastasis of colorectal cancer (pmCRC): identification of predictive molecular signatures by a novel preclinical platform of matching pmCRC PDX/PD3D models. Mol Cancer 20:129

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fisher R, Pusztai L, Swanton C (2013) Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer 108:479–485

    CAS  PubMed  PubMed Central  Google Scholar 

  • Han JY, Kim SH, Lee YS, Lee SY, Hwang JA, Kim JY, Yoon SJ, Lee GK (2014) Comparison of targeted next-generation sequencing with conventional sequencing for predicting the responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in never-smokers with lung adenocarcinoma. Lung Cancer 85:161–167

    PubMed  Google Scholar 

  • Hisamuddin IM, Yang VW (2006) Molecular genetics of colorectal cancer: an overview. Curr Colorectal Cancer Rep 2:53–59

    PubMed  PubMed Central  Google Scholar 

  • Hossain MS, Karuniawati H, Jairoun AA, Urbi Z, Ooi J, John A, Lim YC, Kibria KMK, Mohiuddin AKM, Ming LC et al (2022) Colorectal cancer: a review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers (Basel) 14(7):1732

    PubMed  Google Scholar 

  • Hugen N, van de Velde CJH, de Wilt JHW, Nagtegaal ID (2014) Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol 25:651–657

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jeon Y, Jeon S, Blazyte A, Kim YJ, Lee JJ, Bhak Y, Cho YS, Park Y, Noh EK, Manica A et al (2021) Welfare genome project: a participatory Korean personal genome project with free health check-up and genetic report followed by counseling. Front Genet 12:633731

    PubMed  PubMed Central  Google Scholar 

  • Kamal Y, Schmit SL, Hoehn HJ, Amos CI, Frost HR (2019) Transcriptomic differences between primary colorectal adenocarcinomas and distant metastases reveal metastatic colorectal cancer subtypes. Cancer Res 79:4227–4241

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kang MJ, Jung KW, Bang SH, Choi SH, Park EH, Yun EH, Kim HJ, Kong HJ, Im JS, Seo HG et al (2023) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2020. Cancer Res Treat 55:385–399

    PubMed  PubMed Central  Google Scholar 

  • Khil H, Kim SM, Hong S, Gil HM, Cheon E, Lee DH, Kim YA, Keum N (2021) Time trends of colorectal cancer incidence and associated lifestyle factors in South Korea. Sci Rep 11:2413

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kim CH (2022) Molecular analyses in peritoneal metastasis from colorectal cancer: a review-an English version. J Anus Rectum Colon 6:197–202

    PubMed  PubMed Central  Google Scholar 

  • Kim R, Schell MJ, Teer JK, Greenawalt DM, Yang M, Yeatman TJ (2015) Co-evolution of somatic variation in primary and metastatic colorectal cancer may expand biopsy indications in the molecular era. PLoS ONE 10:e0126670

    PubMed  PubMed Central  Google Scholar 

  • Klaver YL, Lemmens VE, Nienhuijs SW, Luyer MD, de Hingh IH (2012) Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options. World J Gastroenterol 18:5489–5494

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9:302–312

    CAS  PubMed  Google Scholar 

  • Kranenburg O, van der Speeten K, de Hingh I (2021) Peritoneal metastases from colorectal cancer: defining and addressing the challenges. Front Oncol 11:650098

    CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen SG, Goscinski MA, Dueland S, Steigen SE, Hofsli E, Torgunrud A, Lund-Iversen M, Dagenborg VJ, Flatmark K, Sorbye H (2022) Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients. Br J Cancer 126:726–735

    CAS  PubMed  Google Scholar 

  • Larsson C, Cordeddu L, Siggens L, Pandzic T, Kundu S, He L, Ali MA, Pristovsek N, Hartman K, Ekwall K et al (2020) Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression. Clin Epigenetics 12:74

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee SY, Haq F, Kim D, Jun C, Jo HJ, Ahn SM, Lee WS (2014) Comparative genomic analysis of primary and synchronous metastatic colorectal cancers. PLoS ONE 9:e90459

    PubMed  PubMed Central  Google Scholar 

  • Loes IM, Immervoll H, Sorbye H, Angelsen JH, Horn A, Knappskog S, Lonning PE (2016) Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases. Int J Cancer 139:647–656

    CAS  PubMed  PubMed Central  Google Scholar 

  • Merriman B, IonTorrent R, Team D, Rothberg JM (2012) Progress in ion torrent semiconductor chip based sequencing. Electrophoresis 33:3397–3417

    CAS  PubMed  Google Scholar 

  • Mostafaie N, Kallay E, Sauerzapf E, Bonner E, Kriwanek S, Cross HS, Huber KR, Krugluger W (2009) Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer. Mol Carcinog 48:642–647

    CAS  PubMed  Google Scholar 

  • Ohhara Y, Fukuda N, Takeuchi S, Honma R, Shimizu Y, Kinoshita I, Dosaka-Akita H (2016) Role of targeted therapy in metastatic colorectal cancer. World J Gastrointest Oncol 8:642–655

    PubMed  PubMed Central  Google Scholar 

  • Patel SA, Rodrigues P, Wesolowski L, Vanharanta S (2021) Genomic control of metastasis. Br J Cancer 124:3–12

    CAS  PubMed  Google Scholar 

  • Poturnajova M, Furielova T, Balintova S, Schmidtova S, Kucerova L, Matuskova M (2021) Molecular features and gene expression signature of metastatic colorectal cancer (Review). Oncol Rep. https://doi.org/10.3892/or.2021.7961

    Article  PubMed  PubMed Central  Google Scholar 

  • Pretzsch E, Bosch F, Neumann J, Ganschow P, Bazhin A, Guba M, Werner J, Angele M (2019) Mechanisms of metastasis in colorectal cancer and metastatic organotropism: hematogenous versus peritoneal spread. J Oncol 2019:7407190

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rawla P, Sunkara T, Barsouk A (2019) Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 14:89–103

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ren K, Xie X, Min T, Sun T, Wang H, Zhang Y, Dang C, Zhang H (2022) Development of the peritoneal metastasis: a review of back-grounds, mechanisms, treatments and prospects. J Clin Med 12(1):103

    PubMed  PubMed Central  Google Scholar 

  • Shen T, Pajaro-Van de Stadt SH, Yeat NC, Lin JC (2015) Clinical applications of next generation sequencing in cancer: from panels, to exomes, to genomes. Front Genet 6:215

    PubMed  PubMed Central  Google Scholar 

  • Slatko BE, Gardner AF, Ausubel FM (2018) Overview of next-generation sequencing technologies. Curr Protoc Mol Biol 122:e59

    PubMed  PubMed Central  Google Scholar 

  • Starr TK, Scott PM, Marsh BM, Zhao L, Than BL, O’Sullivan MG, Sarver AL, Dupuy AJ, Largaespada DA, Cormier RT (2011) A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proc Natl Acad Sci U S A 108:5765–5770

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E et al (2019) COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res 47:D941–D947

    CAS  PubMed  Google Scholar 

  • Vayrynen V, Wirta EV, Seppala T, Sihvo E, Mecklin JP, Vasala K, Kellokumpu I (2020) Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases: a population-based study. BJS Open 4:685–692

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Zheng X, Wang X, Chen Y, Li Z, Yu J, Yang W, Mao B, Zhang H, Li J et al (2021) Genetic differences between lung metastases and liver metastases from left-sided microsatellite stable colorectal cancer: next generation sequencing and clinical implications. Ann Transl Med 9:967

    CAS  PubMed  PubMed Central  Google Scholar 

  • Worthley DL, Leggett BA (2010) Colorectal cancer: molecular features and clinical opportunities. Clin Biochem Rev 31:31–38

    PubMed  PubMed Central  Google Scholar 

  • Xie YH, Chen YX, Fang JY (2020) Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 5:22

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yin Q, Wang PP, Peng R, Zhou H (2019) MiR-19a enhances cell proliferation, migration, and invasiveness through enhancing lymphangiogenesis by targeting thrombospondin-1 in colorectal cancer. Biochem Cell Biol 97:731–739

    CAS  PubMed  Google Scholar 

  • Zhunussova G, Afonin G, Abdikerim S, Jumanov A, Perfilyeva A, Kaidarova D, Djansugurova L (2019) Mutation spectrum of cancer-associated genes in patients with early onset of colorectal cancer. Front Oncol 9:673

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the Center for Bio-Medical Engineering Core Facility at Dankook University.

Author information

Authors and Affiliations

  1. NGS Clinical Laboratory, Dankook University Hospital, Cheonan, Republic of Korea

    Wonseok Shin, Kyudong Han & Dong-Guk Park

  2. Department of Surgery, Dankook University College of Medicine, Cheonan, Republic of Korea

    Jeongseok Yun & Dong-Guk Park

  3. Department of Microbiology, Dankook University, Cheonan, Republic of Korea

    Kyudong Han

  4. Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, Republic of Korea

    Kyudong Han

  5. R&D Center, HuNbiome Co., Ltd, Seoul, Republic of Korea

    Kyudong Han

Authors
  1. Wonseok Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeongseok Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyudong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong-Guk Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kyudong Han or Dong-Guk Park.

Ethics declarations

Conflict of interest

Wonseok Shin, Jeongseok Yun, Kyudong Han, and Dong-Guk Park declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 16 KB)

Supplementary file2 (XLSX 16 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shin, W., Yun, J., Han, K. et al. Comparison of genetic variation between primary colorectal cancer and metastatic peritoneal cancer. Genes Genom 45, 989–1001 (2023). https://doi.org/10.1007/s13258-023-01408-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-023-01408-3

Keywords

Search

Navigation