Cargando…

Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions

AIM: The aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile se...

Descripción completa

Detalles Bibliográficos
Autores principales: Sugai, Tamotsu, Eizuka, Makoto, Fujita, Yasuko, Kawasaki, Keisuke, Yamamoto, Eiichiro, Ishida, Kazuyuki, Yamano, Hiroo, Suzuki, Hiromu, Matsumoto, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153566/
https://www.ncbi.nlm.nih.gov/pubmed/29974407
http://dx.doi.org/10.1007/s10620-018-5167-4
_version_ 1783357528020615168
author Sugai, Tamotsu
Eizuka, Makoto
Fujita, Yasuko
Kawasaki, Keisuke
Yamamoto, Eiichiro
Ishida, Kazuyuki
Yamano, Hiroo
Suzuki, Hiromu
Matsumoto, Takayuki
author_facet Sugai, Tamotsu
Eizuka, Makoto
Fujita, Yasuko
Kawasaki, Keisuke
Yamamoto, Eiichiro
Ishida, Kazuyuki
Yamano, Hiroo
Suzuki, Hiromu
Matsumoto, Takayuki
author_sort Sugai, Tamotsu
collection PubMed
description AIM: The aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile serrated adenomas/polyps (SSA/Ps), 31 traditional serrated adenomas, and 22 SSA/Ps with cytological dysplasia/adenocarcinoma. METHODS: Mutations in BRAF (V600E)/KRAS (exon 2) and microsatellite status [microsatellite stability (MSS) vs. MSI] were examined using a pyrosequencer and the PCR-based microsatellite method, respectively. DNA methylation status was classified as low (LME), intermediate (IME), or high methylation epigenotype (HME) according to a PCR-based two-step method. In addition, mucin and annexin A10 expression was examined. Finally, we performed a hierarchical clustering analysis of the BRAF/KRAS mutation, DNA methylation, and microsatellite statuses. RESULTS: The molecular patterns observed in the serrated lesions could be divided into five subgroups: lesions characterized by (1) BRAF mutation, HME, and MSI; (2) BRAF mutation, HME, and MSS; (3) BRAF mutation, LME/IME, and MSS; (4) no BRAF/KRAS mutations, LME/IME, and MSS; and (5) KRAS mutation, LME/IME, and MSS. In addition, we demonstrated that these observed molecular patterns help identify the associations of the molecular patterns and markers (i.e., mucin and annexin A10) with the clinicopathological findings, including histological features and histological diagnosis. CONCLUSIONS: We suggest that the identified molecular patterns play an important role in the pathway of serrated lesion development.
format Online
Article
Text
id pubmed-6153566
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-61535662018-10-09 Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions Sugai, Tamotsu Eizuka, Makoto Fujita, Yasuko Kawasaki, Keisuke Yamamoto, Eiichiro Ishida, Kazuyuki Yamano, Hiroo Suzuki, Hiromu Matsumoto, Takayuki Dig Dis Sci Original Article AIM: The aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile serrated adenomas/polyps (SSA/Ps), 31 traditional serrated adenomas, and 22 SSA/Ps with cytological dysplasia/adenocarcinoma. METHODS: Mutations in BRAF (V600E)/KRAS (exon 2) and microsatellite status [microsatellite stability (MSS) vs. MSI] were examined using a pyrosequencer and the PCR-based microsatellite method, respectively. DNA methylation status was classified as low (LME), intermediate (IME), or high methylation epigenotype (HME) according to a PCR-based two-step method. In addition, mucin and annexin A10 expression was examined. Finally, we performed a hierarchical clustering analysis of the BRAF/KRAS mutation, DNA methylation, and microsatellite statuses. RESULTS: The molecular patterns observed in the serrated lesions could be divided into five subgroups: lesions characterized by (1) BRAF mutation, HME, and MSI; (2) BRAF mutation, HME, and MSS; (3) BRAF mutation, LME/IME, and MSS; (4) no BRAF/KRAS mutations, LME/IME, and MSS; and (5) KRAS mutation, LME/IME, and MSS. In addition, we demonstrated that these observed molecular patterns help identify the associations of the molecular patterns and markers (i.e., mucin and annexin A10) with the clinicopathological findings, including histological features and histological diagnosis. CONCLUSIONS: We suggest that the identified molecular patterns play an important role in the pathway of serrated lesion development. Springer US 2018-07-05 2018 /pmc/articles/PMC6153566/ /pubmed/29974407 http://dx.doi.org/10.1007/s10620-018-5167-4 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Sugai, Tamotsu
Eizuka, Makoto
Fujita, Yasuko
Kawasaki, Keisuke
Yamamoto, Eiichiro
Ishida, Kazuyuki
Yamano, Hiroo
Suzuki, Hiromu
Matsumoto, Takayuki
Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title_full Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title_fullStr Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title_full_unstemmed Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title_short Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions
title_sort molecular profiling based on kras/braf mutation, methylation, and microsatellite statuses in serrated lesions
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153566/
https://www.ncbi.nlm.nih.gov/pubmed/29974407
http://dx.doi.org/10.1007/s10620-018-5167-4
work_keys_str_mv AT sugaitamotsu molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT eizukamakoto molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT fujitayasuko molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT kawasakikeisuke molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT yamamotoeiichiro molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT ishidakazuyuki molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT yamanohiroo molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT suzukihiromu molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions
AT matsumototakayuki molecularprofilingbasedonkrasbrafmutationmethylationandmicrosatellitestatusesinserratedlesions