title: MYC deregulation in gastric cancer and its clinicopathological implications.
abstract: Our study investigated the relationship between MYC alterations and clinicopathological features in gastric cancers. We evaluated the effect of MYC mRNA expression and its protein immunoreactivity, as well as copy number variation, promoter DNA methylation, and point mutations, in 125 gastric adenocarcinoma and 67 paried non-neoplastic tissues. We observed that 77% of the tumors presented MYC immunoreactivity which was significantly associated with increased mRNA expression (p<0.05). These observations were associated with deeper tumor extension and the presence of metastasis (p<0.05). MYC protein expression was also more frequently observed in intestinal-type than in diffuse-type tumors (p<0.001). Additionally, MYC mRNA and protein expression were significantly associated with its copy number (p<0.05). The gain of MYC copies was associated with late-onset, intestinal-type, advanced tumor stage, and the presence of distant metastasis (p<0.05). A hypomethylated MYC promoter was detected in 86.4% of tumor samples. MYC hypomethylation was associated with diffuse-type, advanced tumor stage, deeper tumor extension, and the presence of lymph node metastasis (p<0.05). Moreover, eighteen tumor samples presented at least one known mutation. The presence of MYC mutations was associated with diffuse-type tumor (p<0.001). Our results showed that MYC deregulation was mainly associated with poor prognostic features and also reinforced the presence of different pathways involved in intestinal-type and diffuse-type gastric carcinogenesis. Thus, our findings suggest that MYC may be a useful marker for clinical stratification and prognosis.
authors.affiliation: Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil. carolrosalts@gmail.com
authors.forename: Carolina Rosal Teixeira
authors.initials: CR
authors.lastname: de Souza
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.forename: Eliana Kelly
authors.initials: EK
authors.lastname: Costa Sozinho
authors.forename: Bárbara do Nascimento
authors.initials: Bdo N
authors.lastname: Borges
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Andrea Kely Campos Ribeiro
authors.initials: AK
authors.lastname: Dos Santos
authors.forename: Sidney Emanuel Batista
authors.initials: SE
authors.lastname: Dos Santos
authors.forename: Helem Ferreira
authors.initials: HF
authors.lastname: Ribeiro
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.forename: Marília
authors.initials: M
authors.lastname: de Arruda Cardoso Smith
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D017931:DNA Primers; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger