Mucinous adenocarcinoma of the colon and rectum: A genomic analysis.
Adenocarcinoma
/ genetics
Adenocarcinoma, Mucinous
/ genetics
Cohort Studies
Colonic Neoplasms
/ genetics
DNA Copy Number Variations
DNA-Binding Proteins
/ genetics
Datasets as Topic
Gene Expression Regulation, Neoplastic
Genomics
Humans
INDEL Mutation
Microsatellite Instability
Mucins
/ genetics
Mutation
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins B-raf
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
Rectal Neoplasms
/ genetics
Smad4 Protein
/ genetics
Transforming Growth Factor beta
/ genetics
Tumor Suppressor Protein p53
/ genetics
colorectal cancer
mucinous adenocarcinoma
oncogenetics
Journal
Journal of surgical oncology
ISSN: 1096-9098
Titre abrégé: J Surg Oncol
Pays: United States
ID NLM: 0222643
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
08
10
2019
accepted:
04
11
2019
pubmed:
16
11
2019
medline:
4
12
2019
entrez:
16
11
2019
Statut:
ppublish
Résumé
Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC. Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken. Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-β, and TP53 pathways. Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC.
METHODS
METHODS
Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken.
RESULTS
RESULTS
Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-β, and TP53 pathways.
CONCLUSIONS
CONCLUSIONS
Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.
Substances chimiques
DNA-Binding Proteins
0
G-T mismatch-binding protein
0
KRAS protein, human
0
Mucins
0
SMAD4 protein, human
0
Smad4 Protein
0
TP53 protein, human
0
Transforming Growth Factor beta
0
Tumor Suppressor Protein p53
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1427-1435Subventions
Organisme : Beaumont Hospital Colorectal Research Fund; Science Foundation Ireland
ID : 15/ERA-CSM/3268
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
American Cancer Society. Key statistics for colorectal cancer. 2017.
Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21:1350-1356.
UK Cr. Bowel cancer statistics. 2018.
Sung H, Siegel RL, Rosenberg PS, Jemal A. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. Lancet Public Health. 2019;4:e137-e147.
Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017;109.
Kang H, O'Connell JB, Maggard MA, Sack J, Ko CY. A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum. 2005;48:1161-1168.
Hamilton SR, Aaltonen LA, eds. World Health Organization Classification of Tumours. Lyon, France: IARC Press; 2000.
McCawley N, Clancy C, O'Neill BDP, Deasy J, McNamara DA, Burke JP. Mucinous rectal adenocarcinoma is associated with a poor response to neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Dis Colon Rectum. 2016;59:1200-1208.
Debunne H, Ceelen W. Mucinous differentiation in colorectal cancer: molecular, histological and clinical aspects. Acta Chir Belg. 2013;113:385-390.
Song G, Deng G, Bell I, Kakar S, Sleisenger M, Kim Y. Mucinous carcinomas of the colorectum have distinct molecular genetic characteristics. Int J Oncol. 2005;26:745-750.
Albanese I, Rinaudo C, Alberti M, et al. ras and myc analysis in primary and metastatic colorectal carcinomas. Int J Oncol. 1997;10:293-300.
Bazan V. Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol. 2002;13:1438-1446.
Liddell C, Droy-Dupré L, Métairie S, et al. Mapping clinicopathological entities within colorectal mucinous adenocarcinomas: a hierarchical clustering approach. Mod Pathol. 2017;30:1177-1189.
Jang MH, Kim S, Hwang DY, et al. BRAF-mutated colorectal cancer exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability status. J Korean Med Sci. 2017;32:38-46.
Andrici J, Farzin M, Sioson L, et al. Mismatch repair deficiency as a prognostic factor in mucinous colorectal cancer. Mod Pathol. 2016;29:266-274.
Inamura K, Yamauchi M, Nishihara R, et al. Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol. 2015;22:1226-1235.
Reynolds IS, Furney SJ, Kay EW, McNamara DA, Prehn JHM, Burke JP. Meta-analysis of the molecular associations of mucinous colorectal cancer. Br J Surg. 2019;106:682-691.
Luzzatto L. Somatic mutations in cancer development. Environ Health. 2011;10(suppl 1):S12.
Stanley R, Hamilton LAA. World Health Organization Classification of Tumours-Pathology and Genetics of Tumours of the Digestive System. Lyon, France: IARC Press; 2000.
Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell. 2018;173:321.e10-337.e10.
Wang C, Liang C. MSIpred: a python package for tumor microsatellite instability classification from tumor mutation annotation data using a support vector machine. Sci Rep. 2018;8. 17546.
Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018;28:1747-1756.
Puca L, Chastagner P, Meas-Yedid V, Israel A, Brou C. A-arrestin 1 (ARRDC1) and β-arrestins cooperate to mediate Notch degradation in mammals. J Cell Sci. 2013;126:4457-4468.
Julien LA, Carriere A, Moreau J, Roux PP. mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling. Mol Cell Biol. 2010;30:908-921.
Sarbassov DD. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098-1101.
Sarbassov DD, Ali SM, Kim DH, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14:1296-1302.
Csukasi F, Duran I, Barad M, et al. The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling. Sci Transl Med. 2018;10. eaat9356.
Wang JQ, Chen JH, Chen YC, et al. Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains. PLoS One. 2013;8:e65586.
Kulkarni SV, Gish G, van der Geer P, Henkemeyer M, Pawson T. Role of p120 Ras-GAP in directed cell movement. J Cell Biol. 2000;149:457-470.
Fodde R. The APC gene in colorectal cancer. Eur J Cancer. 2002;38:867-871.
Goss KH, Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol. 2000;18:1967-1979.
Hugen N, Simons M, Halilović A, et al. The molecular background of mucinous carcinoma beyond MUC2. J Pathol Clin Res. 2015;1:3-17.
Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386-1422.
Au TH, Wang K, Stenehjem D, Garrido-Laguna I. Personalized and precision medicine: integrating genomics into treatment decisions in gastrointestinal malignancies. J Gastrointest Oncol. 2017;8:387-404.
Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182-1191.
Chouhan H, Sammour T, Thomas ML, Moore JW. The interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival outcomes after adjuvant 5FU based chemotherapy in stage III colon cancer. J Surg Oncol. 2018;118:1311-1317.
Van Cutsem E, Huijberts S, Grothey A, et al. Binimetinib, encorafenib, and cetuximab triplet therapy for patients with BRAF V600E-mutant metastatic colorectal cancer: safety lead-in results from the phase III BEACON colorectal cancer study. J Clin Oncol. 2019;37:1460-1469.
Ciombor KK, Goldberg RM. Hypermutated tumors and immune checkpoint inhibition. Drugs. 2018;78:155-162.
Nebot-Bral L, Brandao D, Verlingue L, et al. Hypermutated tumours in the era of immunotherapy: the paradigm of personalised medicine. Eur J Cancer. 2017;84:290-303.
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759-767.
Carethers JM. Microsatellite instability pathway and EMAST in colorectal cancer. Curr Colorectal Cancer Rep. 2017;13:73-80.
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JPJ. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A. 1999;96:8681-8686.