Dataset Information

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

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).

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.

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).

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.

SUBMITTER: Konda K

PROVIDER: S-EPMC4122357 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

Konda Kenichi K Konishi Kazuo K Yamochi Toshiko T Ito Yoichi M YM Nozawa Hisako H Tojo Masayuki M Shinmura Kensuke K Kogo Mari M Katagiri Atsushi A Kubota Yutaro Y Muramoto Takashi T Yano Yuichiro Y Kobayashi Yoshiya Y Kihara Toshihiro T Tagawa Teppei T Makino Reiko R Takimoto Masafumi M Imawari Michio M Yoshida Hitoshi H

PloS one 20140805 8

<h4>Background</h4>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).<h4>Methods</h4>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] marke ...[more]

PMID: 25093594

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Dataset Information

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

Background

Methods

Results

Conclusion

Publications

Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

Similar Datasets

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