Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohorts
2.2. Extraction of DNA and RNA from Tissue
2.3. Analysis of EMAST and MSI
2.4. Analysis of Gene Methylation and Gene Expression
2.5. Statistical Analysis
2.6. Analysis of The Cancer Genome Atlas (TCGA) Dataset
3. Results
3.1. Patterns of EMAST Marker Positivity Are Different between Colorectal and Pancreatic Carcinomas
3.2. EMAST≥3/5 Is Associated with MSI-H Across Different Cancer Types
3.3. Presence of a Single EMAST Marker Is Associated with MSI-L and Lymph Node Metastases But Not Location in Sporadic Colorectal Carcinoma
3.4. EMAST-1/5 Colorectal Cancers Show Only Scattered Methylation
3.5. Presence of 1–2 EMAST Markers Is Not Associated with Down-Regulation of MSH3 mRNA Expression
3.6. MSH3 Gene Mutations Are Rare But Copy Number Alterations Are More Common in Colorectal and Pancreatic Carcinoma
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Fishel, R. The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: Revising the mutator hypothesis. Cancer Res. 2001, 61, 7369–7374. [Google Scholar]
- Boland, C.R.; Goel, A. Microsatellite instability in colorectal cancer. Gastroenterology 2010, 138, 2073–2087.e2073. [Google Scholar] [CrossRef]
- Boland, C.R.; Thibodeau, S.N.; Hamilton, S.R.; Sidransky, D.; Eshleman, J.R.; Burt, R.W.; Meltzer, S.J.; Rodriguez-Bigas, M.A.; Fodde, R.; Ranzani, G.N.; et al. A national cancer institute workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998, 58, 5248–5257. [Google Scholar]
- Carethers, J.M.; Koi, M.; Tseng-Rogenski, S.S. Emast is a form of microsatellite instability that is initiated by inflammation and modulates colorectal cancer progression. Genes 2015, 6, 185–205. [Google Scholar] [CrossRef] [Green Version]
- Tseng-Rogenski, S.S.; Hamaya, Y.; Choi, D.Y.; Carethers, J.M. Interleukin 6 alters localization of hmsh3, leading to DNA mismatch repair defects in colorectal cancer cells. Gastroenterology 2015, 148, 579–589. [Google Scholar] [CrossRef] [Green Version]
- Yamada, K.; Kanazawa, S.; Koike, J.; Sugiyama, H.; Xu, C.; Funahashi, K.; Boland, C.R.; Koi, M.; Hemmi, H. Microsatellite instability at tetranucleotide repeats in sporadic colorectal cancer in japan. Oncol. Rep. 2010, 23, 551–561. [Google Scholar]
- Haugen, A.C.; Goel, A.; Yamada, K.; Marra, G.; Nguyen, T.P.; Nagasaka, T.; Kanazawa, S.; Koike, J.; Kikuchi, Y.; Zhong, X.; et al. Genetic instability caused by loss of muts homologue 3 in human colorectal cancer. Cancer Res. 2008, 68, 8465–8472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, S.Y.; Chung, H.; Devaraj, B.; Iwaizumi, M.; Han, H.S.; Hwang, D.Y.; Seong, M.K.; Jung, B.H.; Carethers, J.M. Microsatellite alterations at selected tetranucleotide repeats are associated with morphologies of colorectal neoplasias. Gastroenterology 2010, 139, 1519–1525. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Devaraj, B.; Lee, A.; Cabrera, B.L.; Miyai, K.; Luo, L.; Ramamoorthy, S.; Keku, T.; Sandler, R.S.; McGuire, K.L.; Carethers, J.M. Relationship of emast and microsatellite instability among patients with rectal cancer. J. Gastrointest Surg 2010, 14, 1521–1528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Munakata, K.; Koi, M.; Kitajima, T.; Tseng-Rogenski, S.; Uemura, M.; Matsuno, H.; Kawai, K.; Sekido, Y.; Mizushima, T.; Toiyama, Y.; et al. Inflammation-associated microsatellite alterations caused by msh3 dysfunction are prevalent in ulcerative colitis and increase with neoplastic advancement. Clin. Transl. Gastroenterol. 2019, 10, e00105. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.G.; Lee, S.; Kim, D.Y.; Ryu, S.Y.; Joo, J.K.; Kim, J.C.; Lee, K.H.; Lee, J.H. Aberrant methylation of DNA mismatch repair genes in elderly patients with sporadic gastric carcinoma: A comparison with younger patients. J. Surg. Oncol. 2010, 101, 28–35. [Google Scholar] [CrossRef]
- Garcia, M.; Choi, C.; Kim, H.R.; Daoud, Y.; Toiyama, Y.; Takahashi, M.; Goel, A.; Boland, C.R.; Koi, M. Association between recurrent metastasis from stage ii and iii primary colorectal tumors and moderate microsatellite instability. Gastroenterology 2012, 143, 48–50.e41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raeker, M.O.; Pierre-Charles, J.; Carethers, J.M. Tetranucleotide microsatellite mutational behavior assessed in real time: Implications for future microsatellite panels. Cell Mol. Gastroenterol. Hepatol. 2020, 9, 689–704. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Toyota, M.; Ahuja, N.; Ohe-Toyota, M.; Herman, J.G.; Baylin, S.B.; Issa, J.P. Cpg island methylator phenotype in colorectal cancer. Proc. Natl. Acad. Sci. USA 1999, 96, 8681–8686. [Google Scholar] [CrossRef] [Green Version]
- Juo, Y.Y.; Johnston, F.M.; Zhang, D.Y.; Juo, H.H.; Wang, H.; Pappou, E.P.; Yu, T.; Easwaran, H.; Baylin, S.; van Engeland, M.; et al. Prognostic value of cpg island methylator phenotype among colorectal cancer patients: A systematic review and meta-analysis. Ann. Oncol. 2014, 25, 2314–2327. [Google Scholar] [CrossRef] [PubMed]
- Jover, R.; Nguyen, T.P.; Perez-Carbonell, L.; Zapater, P.; Paya, A.; Alenda, C.; Rojas, E.; Cubiella, J.; Balaguer, F.; Morillas, J.D.; et al. 5-fluorouracil adjuvant chemotherapy does not increase survival in patients with cpg island methylator phenotype colorectal cancer. Gastroenterology 2011, 140, 1174–1181. [Google Scholar] [CrossRef] [Green Version]
- Weisenberger, D.J.; Siegmund, K.D.; Campan, M.; Young, J.; Long, T.I.; Faasse, M.A.; Kang, G.H.; Widschwendter, M.; Weener, D.; Buchanan, D.; et al. Cpg island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with braf mutation in colorectal cancer. Nat. Genet. 2006, 38, 787–793. [Google Scholar] [CrossRef]
- Kohonen-Corish, M.R.; Sigglekow, N.D.; Susanto, J.; Chapuis, P.H.; Bokey, E.L.; Dent, O.F.; Chan, C.; Lin, B.P.; Seng, T.J.; Laird, P.W.; et al. Promoter methylation of the mutated in colorectal cancer gene is a frequent early event in colorectal cancer. Oncogene 2007, 26, 4435–4441. [Google Scholar] [CrossRef] [Green Version]
- Kohonen-Corish, M.R.; Tseung, J.; Chan, C.; Currey, N.; Dent, O.F.; Clarke, S.; Bokey, L.; Chapuis, P.H. Kras mutations and cdkn2a promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer. Int. J. Cancer. 2014, 134, 2820–2828. [Google Scholar] [CrossRef]
- Benthani, F.A.; Herrmann, D.; Tran, P.N.; Pangon, L.; Lucas, M.C.; Allam, A.H.; Currey, N.; Al-Sohaily, S.; Giry-Laterriere, M.; Warusavitarne, J.; et al. “Mcc” protein interacts with e-cadherin and beta-catenin strengthening cell-cell adhesion of hct116 colon cancer cells. Oncogene 2018, 37, 663–672. [Google Scholar] [CrossRef]
- Currey, N.; Jahan, Z.; Caldon, C.E.; Tran, P.N.; Benthani, F.; De Lacavalerie, P.; Roden, D.L.; Gloss, B.S.; Campos, C.; Bean, E.G.; et al. Mouse model of mutated in colorectal cancer gene deletion reveals novel pathways in inflammation and cancer. Cell Mol. Gastroenterol. Hepatol. 2019, 7, 819–839. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pangon, L.; Sigglekow, N.D.; Larance, M.; Al-Sohaily, S.; Mladenova, D.N.; Selinger, C.I.; Musgrove, E.A.; Kohonen-Corish, M.R. The “mutated in colorectal cancer” protein is a novel target of the uv-induced DNA damage checkpoint. Genes Cancer 2010, 1, 917–926. [Google Scholar] [CrossRef] [Green Version]
- Pangon, L.; Van Kralingen, C.; Abas, M.; Daly, R.J.; Musgrove, E.A.; Kohonen-Corish, M.R. The pdz-binding motif of mcc is phosphorylated at position -1 and controls lamellipodia formation in colon epithelial cells. Biochim. Biophys. Acta 2012, 1823, 1058–1067. [Google Scholar] [CrossRef] [Green Version]
- Al-Sohaily, S.; Henderson, C.; Selinger, C.; Pangon, L.; Segelov, E.; Kohonen-Corish, M.R.; Warusavitarne, J. Loss of special at-rich sequence-binding protein 1 (satb1) predicts poor survival in patients with colorectal cancer. Histopathology 2014, 65, 155–163. [Google Scholar] [CrossRef] [PubMed]
- Jenkins, M.A.; Win, A.K.; Templeton, A.S.; Angelakos, M.S.; Buchanan, D.D.; Cotterchio, M.; Figueiredo, J.C.; Thibodeau, S.N.; Baron, J.A.; Potter, J.D.; et al. Cohort profile: The colon cancer family registry cohort (ccfrc). Int. J. Epidemiol. 2018, 47, 387–388i. [Google Scholar] [CrossRef] [PubMed]
- Newcomb, P.A.; Baron, J.; Cotterchio, M.; Gallinger, S.; Grove, J.; Haile, R.; Hall, D.; Hopper, J.L.; Jass, J.; Le Marchand, L.; et al. Colon cancer family registry: An international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol. Biomark. Prev. 2007, 16, 2331–2343. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buchanan, D.D.; Clendenning, M.; Rosty, C.; Eriksen, S.V.; Walsh, M.D.; Walters, R.J.; Thibodeau, S.N.; Stewart, J.; Preston, S.; Win, A.K.; et al. Tumor testing to identify lynch syndrome in two australian colorectal cancer cohorts. J. Gastroenterol. Hepatol. 2017, 32, 427–438. [Google Scholar] [CrossRef] [Green Version]
- Sigglekow, N.D.; Pangon, L.; Brummer, T.; Molloy, M.; Hawkins, N.J.; Ward, R.L.; Musgrove, E.A.; Kohonen-Corish, M.R. Mutated in colorectal cancer protein modulates the nfkappab pathway. Anticancer Res. 2012, 32, 73–79. [Google Scholar]
- Humphris, J.L.; Patch, A.M.; Nones, K.; Bailey, P.J.; Johns, A.L.; McKay, S.; Chang, D.K.; Miller, D.K.; Pajic, M.; Kassahn, K.S.; et al. Hypermutation in pancreatic cancer. Gastroenterology 2017, 152, 68–74.e62. [Google Scholar] [CrossRef] [Green Version]
- Biankin, A.V.; Waddell, N.; Kassahn, K.S.; Gingras, M.C.; Muthuswamy, L.B.; Johns, A.L.; Miller, D.K.; Wilson, P.J.; Patch, A.M.; Wu, J.; et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012, 491, 399–405. [Google Scholar] [CrossRef] [PubMed]
- Kohonen-Corish, M.R.; Daniel, J.J.; Chan, C.; Lin, B.P.; Kwun, S.Y.; Dent, O.F.; Dhillon, V.S.; Trent, R.J.; Chapuis, P.H.; Bokey, E.L. Low microsatellite instability is associated with poor prognosis in stage c colon cancer. J. Clin. Oncol. 2005, 23, 2318–2324. [Google Scholar] [CrossRef] [PubMed]
- Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; et al. The cbio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012, 2, 401–404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; et al. Integrative analysis of complex cancer genomics and clinical profiles using the cbioportal. Sci. Signal. 2013, 6, pl1. [Google Scholar] [CrossRef] [Green Version]
- Hoadley, K.A.; Yau, C.; Hinoue, T.; Wolf, D.M.; Lazar, A.J.; Drill, E.; Shen, R.; Taylor, A.M.; Cherniack, A.D.; Thorsson, V.; et al. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 2018, 173, 291–304.e296. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bonneville, R.; Krook, M.A.; Kautto, E.A.; Miya, J.; Wing, M.R.; Chen, H.Z.; Reeser, J.W.; Yu, L.; Roychowdhury, S. Landscape of microsatellite instability across 39 cancer types. JCO Precis. Oncol. 2017, 2017. [Google Scholar] [CrossRef]
- Li, Y.; Ge, D.; Lu, C. The smart app: An interactive web application for comprehensive DNA methylation analysis and visualization. Epigenetics. Chromatin 2019, 12, 71. [Google Scholar] [CrossRef] [Green Version]
- Torshizi Esfahani, A.; Seyedna, S.Y.; Nazemalhosseini Mojarad, E.; Majd, A.; Asadzadeh Aghdaei, H. Msi-l/emast is a predictive biomarker for metastasis in colorectal cancer patients. J. Cell Physiol. 2019, 234, 13128–13136. [Google Scholar] [CrossRef]
- Plaschke, J.; Preussler, M.; Ziegler, A.; Schackert, H.K. Aberrant protein expression and frequent allelic loss of msh3 in colorectal cancer with low-level microsatellite instability. Int. J. Colorectal Dis. 2012, 27, 911–919. [Google Scholar] [CrossRef]
- Tseng-Rogenski, S.S.; Chung, H.; Wilk, M.B.; Zhang, S.; Iwaizumi, M.; Carethers, J.M. Oxidative stress induces nuclear-to-cytosol shift of hmsh3, a potential mechanism for emast in colorectal cancer cells. PLoS ONE 2012, 7, e50616. [Google Scholar] [CrossRef] [Green Version]
- Goel, A.; Nagasaka, T.; Arnold, C.N.; Inoue, T.; Hamilton, C.; Niedzwiecki, D.; Compton, C.; Mayer, R.J.; Goldberg, R.; Bertagnolli, M.M.; et al. The cpg island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology 2007, 132, 127–138. [Google Scholar] [CrossRef]
- Mori, T.; Hamaya, Y.; Uotani, T.; Yamade, M.; Iwaizumi, M.; Furuta, T.; Miyajima, H.; Osawa, S.; Sugimoto, K. Prevalence of elevated microsatellite alterations at selected tetranucleotide repeats in pancreatic ductal adenocarcinoma. PLoS ONE 2018, 13, e0208557. [Google Scholar] [CrossRef] [PubMed]
- Van Duijneveldt, G.; Griffin, M.D.W.; Putoczki, T.L. Emerging roles for the il-6 family of cytokines in pancreatic cancer. Clin. Sci. 2020, 134, 2091–2115. [Google Scholar] [CrossRef] [PubMed]
- Koi, M.; Tseng-Rogenski, S.S.; Carethers, J.M. Inflammation-associated microsatellite alterations: Mechanisms and significance in the prognosis of patients with colorectal cancer. World J. Gastrointest. Oncol. 2018, 10, 1–14. [Google Scholar] [CrossRef]
- Pirini, F.; Pasini, L.; Tedaldi, G.; Scarpi, E.; Marisi, G.; Molinari, C.; Calistri, D.; Passardi, A.; Ulivi, P. Instability of non-standard microsatellites in relation to prognosis in metastatic colorectal cancer patients. Int. J. Mol. Sci. 2020, 21, 3532. [Google Scholar] [CrossRef]
- Kondelin, J.; Martin, S.; Katainen, R.; Renkonen-Sinisalo, L.; Lepisto, A.; Koskensalo, S.; Bohm, J.; Mecklin, J.P.; Cajuso, T.; Hanninen, U.A.; et al. No evidence of emast in whole genome sequencing data from 248 colorectal cancers. Genes Chromosomes Cancer 2021, 60, 463–473. [Google Scholar] [CrossRef] [PubMed]
- Venderbosch, S.; van Lent-van Vliet, S.; de Haan, A.F.; Ligtenberg, M.J.; Goossens, M.; Punt, C.J.; Koopman, M.; Nagtegaal, I.D. Emast is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer. PLoS ONE 2015, 10, e0124538. [Google Scholar] [CrossRef]
- Ahrendt, S.A.; Decker, P.A.; Doffek, K.; Wang, B.; Xu, L.; Demeure, M.J.; Jen, J.; Sidransky, D. Microsatellite instability at selected tetranucleotide repeats is associated with p53 mutations in non-small cell lung cancer. Cancer Res. 2000, 60, 2488–2491. [Google Scholar]
- Dietlein, F.; Thelen, L.; Reinhardt, H.C. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches. Trends Genet. 2014, 30, 326–339. [Google Scholar] [CrossRef]
Tumour Feature | Variable | EMAST- ≥3/5 n = 13 (%) | EMAST- 2/5 n = 16 (%) | EMAST- 1/5 n = 26 (%) | No EMAST n = 45 (%) | p ** |
---|---|---|---|---|---|---|
Microsatellite instability | MSS | 2 (3) | 13 (17) | 17 (23) | 42 (57) | <0.0001 |
MSI-L | 0 (0) | 2 (15) | 9 (70) | 2 (15) | ||
MSI-H | 11 (84) | 1 (8) | 0 (0) | 1 (8) | ||
CIMP | Absent | 3 (5) | 8 (14) | 21 (37) | 25 (44) | <0.0001 |
CIMP-L | 2 (7) | 6 (20) | 4 (13) | 18 (60) | ||
CIMP-H | 8 (62) | 2 (15) | 1 (8) | 2 (15) | ||
CDKN2A (p16) methylation | Absent | 5 (7) | 11 (15) | 22 (29) | 37 (49) | 0.007 |
Present | 8 (32) | 5 (20) | 4 (16) | 8 (32) | ||
MCC methylation | Absent | 4 (6) | 9 (13) | 22 (31) | 35 (50) | 0.002 |
Present | 9 (31) | 6 (21) | 4 (14) | 10 (34) | ||
CDKN2A & MCC methylation | Absent | 5(5) | 11 (13) | 25 (31) | 41 (51) | <0.00001 |
Present | 8 (44) | 5* (28) | 1 * (6) | 4 (22) | ||
Dukes stage | 1,2 | 10 (17) | 8 (14) | 8 (14) | 32 (55) | 0.028 |
3 | 2 (7) | 6 (21) | 11 (39) | 9 (32) | ||
4 | 1 (7) | 2 (14) | 7 (50) | 4 (29) | ||
T stage | 1,2 | 2 (7) | 5 (19) | 6 (22) | 14 (52) | 0.654 |
3,4 | 11 (15) | 11 (15) | 20 (27) | 31 (43) | ||
N stage | 0 | 10 (16) | 8 (13) | 10 (16) | 33 (54) | 0.036 |
1 | 1 (5) | 4 (19) | 7 (33) | 9 (43) | ||
2 | 2 (11) | 4 (22) | 9 (50) | 3 (17) | ||
M stage | 0 | 12 (14) | 14 (16) | 20 (23) | 41 (47) | 0.343 |
1 | 1 (8) | 2 (15) | 6 (46) | 4 (31) | ||
Tumour site | Proximal | 11 (31) | 6 (17) | 7 (19) | 12 (33) | 0.004 |
Distal | 1 (3) | 8 (23) | 9 (26) | 17 (48) | ||
Rectum | 1 (3) | 2 (7) | 10 (34) | 16 (55) | ||
Tumour size (median = 47) | <47 mm | 2 (4) | 9 (19) | 8 (17) | 29 (60) | 0.002 |
≥47 mm | 11 (22) | 7 (14) | 17 (35) | 14 (29) | ||
Sex | Female | 6 (12) | 7 (14) | 16 (33) | 20 (41) | 0.526 |
Male | 7 (14) | 9 (17) | 10 (20) | 25 (49) | ||
Differentiation | Well/ Moderate | 9 (10) | 14 (16) | 23 (27) | 40 (47) | 0.636 |
Poor | 3 (23) | 2 (15) | 3 (23) | 5 (38) |
Tumour Feature | Variable | MSI-H n = 13 (%) | MSI-L n = 13 (%) | MSS n = 74 (%) | p * |
---|---|---|---|---|---|
Number of EMAST markers | 0 | 1 (2) | 2 (4) | 42 (93) | <0.0001 |
1–2 | 1 (2) | 11 (26) | 30 (71) | - | |
3–5 | 11 (85) | 0 (0) | 2 (15) | - | |
CIMP | Absent | 4 (7) | 10 (18) | 43 (75) | 0.003 |
CIMP-L | 3 (10) | 3 (10) | 24 (80) | - | |
CIMP-H | 6 (46) | 0 (0) | 7 (54) | - | |
CDKN2A (p16) methylation | Absent | 7 (9) | 12 (16) | 56 (75) | 0.014 |
Present | 6 (24) | 1 (4) | 18 (72) | - | |
MCC methylation | Absent | 6 (8) | 11 (16) | 53 (76) | 0.004 |
Present | 7 (24) | 1 (3) | 21 (72) | - | |
CDKN2A & MCC methylation | Absent | 7 (8) | 13 (16) | 62 (76) | 0.007 |
Present | 6 (33) | 0 (0) | 12 (67) | - | |
Dukes stage | 1.2 | 11 (19) | 2 (3) | 45 (78) | 0.007 |
3 | 2 (7) | 7 (25) | 19 (68) | - | |
4 | 0 (0) | 4 (29) | 10 (71) | - | |
T stage | 1,2 | 3 (11) | 4 (15) | 20 (74) | 0.907 |
3,4 | 10 (14) | 9 (12) | 54 (74) | - | |
N stage | 0 | 11 (18) | 4 (7) | 46 (75) | 0.019 |
1,2 | 2 (5) | 9 (23) | 28 (72) | - | |
M stage | 0 | 13 (15) | 10 (11) | 64 (74) | 0.190 |
1 | 0 (0) | 3 (23) | 10 (77) | - | |
Tumour site | Proximal | 10 (28) | 1 (3) | 25 (69) | 0.006 |
Distal | 2 (6) | 7 (20) | 26 (74) | - | |
Rectum | 1 (3) | 5 (17) | 23 (79) | - | |
Tumour size | <47 mm | 4 (8) | 8 (17) | 36 (75) | 0.270 |
≥47 mm | 9 (18) | 5 (10) | 35 (71) | - | |
Sex | Female | 6 (12) | 6 (12) | 37 (76) | 0.944 |
Male | 7 (14) | 7 (14) | 37 (72) | - | |
Differentiation | Well/ Moderate | 10 (12) | 12 (14) | 64 (74) | 0.787 |
Poor | 2 (15) | 1 (8) | 10 (77) | - |
Tumour Feature | Variable | MSH3 mRNA Expression <0.63 n = 48 (%) | MSH3 mRNA Expression ≥0.63 n = 48 (%) | p * |
---|---|---|---|---|
Microsatellite instability | H | 10 (77) | 3 (23) | 0.006 |
L | 2 (15) | 11 (85) | - | |
S | 36 (51) | 34 (49) | - | |
EMAST | ≥3/5 | 11 (85) | 2 (15) | 0.011 |
1–2/5 | 21 (51) | 20 (49) | - | |
0/5 | 16 (38) | 26 (62) | - | |
CIMP | H | 11 (85) | 2 (15) | 0.006 |
L | 17 (57) | 13 (43) | - | |
Absent | 20 (38) | 33 (62) | - | |
CDKN2A (p16) methylation | Yes | 16 (67) | 8 (33) | 0.098 |
No | 32 (44) | 40 (56) | - | |
MCC methylation | Yes | 23 (82) | 5 (18) | 0.0001 |
No | 25 (37) | 42 (63) | - |
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Meessen, S.; Currey, N.; Jahan, Z.; Parker, H.W.; Jenkins, M.A.; Buchanan, D.D.; Hopper, J.L.; Segelov, E.; Dahlstrom, J.E.; Kohonen-Corish, M.R.J. Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer. Cancers 2021, 13, 3529. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143529
Meessen S, Currey N, Jahan Z, Parker HW, Jenkins MA, Buchanan DD, Hopper JL, Segelov E, Dahlstrom JE, Kohonen-Corish MRJ. Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer. Cancers. 2021; 13(14):3529. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143529
Chicago/Turabian StyleMeessen, Sabine, Nicola Currey, Zeenat Jahan, Hannah W. Parker, Mark A. Jenkins, Daniel D. Buchanan, John L. Hopper, Eva Segelov, Jane E. Dahlstrom, and Maija R. J. Kohonen-Corish. 2021. "Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer" Cancers 13, no. 14: 3529. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143529