title: Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.
abstract: Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinoma cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.
authors.affiliation: Department of Pathology, University of Campinas/UNICAMP, Campinas, Brazil.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Costa
authors.affiliation: Department of Pathology, University of Campinas/UNICAMP, Campinas, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
authors.affiliation: Department of Otolaryngology, IUOPA Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Inclán
authors.affiliation: Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Florentino
authors.initials: F
authors.lastname: Fresno
authors.affiliation: Department of Otolaryngology, IUOPA Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Department of Otolaryngology, IUOPA Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Llorente
authors.affiliation: Department of Otolaryngology, IUOPA Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Hermsen
mesh_terms: D000328:Adult; D003528:Carcinoma, Adenoid Cystic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D054337:Cell Dedifferentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020570:Genes, myb / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics
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