title: A novel case of rhabdoid colon carcinoma associated with a positive CpG island methylator phenotype and BRAF mutation.
abstract: Colon carcinoma with rhabdoid characteristics is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a colon adenocarcinoma with rhabdoid features in a 71-year-old woman, localized to the right colon and associated with local lymph node and liver metastasis. The patient died within 8 months from surgery despite target chemotherapy. The tumor was enriched in cells with a typical rhabdoid-type morphology displaying a marked and diffuse vimentin staining. Cells were also positive for epidermal growth factor receptor (EGFR), p53, Ki67, and β-catenin and negative for cytokeratin 20/cytokeratin 7, E-cadherin, and CDX2. Remarkably, the promoter regions of 4 of 5 specific genes that define the so-called "CpG island methylator phenotype," including mutL homolog 1 (MLH1), were methylated. Consistently, microsatellite instability was detected. A BRAF V600E mutation and no KRAS mutations were identified. Finally, 4 tumor suppressor gene promoters CDH1, CDKN1B, CDKN1C, and MGMT were not methylated. This is the first case of a colorectal carcinoma with rhabdoid features, "CpG island methylator phenotype," high microsatellite instability associated with a BRAF mutation, and patient poorer outcome.
authors.affiliation: Department of Biological and Environmental Sciences, University of Sannio, 82100 Benevento, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pancione
authors.forename: Arturo
authors.initials: A
authors.lastname: Di Blasi
authors.forename: Lina
authors.initials: L
authors.lastname: Sabatino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fucci
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Dalena
authors.forename: Natalia
authors.initials: N
authors.lastname: Palombi
authors.forename: Pietro
authors.initials: P
authors.lastname: Carotenuto
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aquino
authors.forename: Bruno
authors.initials: B
authors.lastname: Daniele
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colantuoni
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D053842:Microsatellite Instability; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018335:Rhabdoid Tumor / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf