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Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.
- Source :
-
PloS one [PLoS One] 2014 Aug 05; Vol. 9 (8), pp. e103822. Date of Electronic Publication: 2014 Aug 05 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Background: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).<br />Methods: We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.<br />Results: S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41).<br />Conclusion: We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.
- Subjects :
- Adenoma classification
Adult
Aged
Aged, 80 and over
Class I Phosphatidylinositol 3-Kinases
Cohort Studies
Colorectal Neoplasms classification
DNA Methylation
Female
Humans
Male
Microsatellite Instability
Middle Aged
Mutation
Phosphatidylinositol 3-Kinases genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins p21(ras)
Tumor Suppressor Protein p53 genetics
ras Proteins genetics
Adenoma genetics
Adenoma pathology
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
DNA Mutational Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25093594
- Full Text :
- https://doi.org/10.1371/journal.pone.0103822