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Studies of genomic imbalances and the MYB-NFIB gene fusion in polymorphous low-grade adenocarcinoma of the head and neck.

Journal article
Authors Fredrik Persson
Andre Fehr
Kaarina Sundelin
Bernd Schulte
Thomas Löning
Göran Stenman
Published in International journal of oncology
Volume 40
Issue 1
Pages 80-4
ISSN 1791-2423
Publication year 2012
Published at Institute of Biomedicine, Department of Pathology
Sahlgrenska Cancer Center
Pages 80-4
Language en
Links dx.doi.org/10.3892/ijo.2011.1190
Keywords Adenocarcinoma, genetics, metabolism, pathology, Adolescent, Adult, Aged, Aged, 80 and over, Chromosome Aberrations, Comparative Genomic Hybridization, Female, Gene Dosage, Head and Neck Neoplasms, genetics, metabolism, pathology, Humans, Male, Neoplasm Grading, Oncogene Proteins, Fusion, biosynthesis, genetics, Polymerase Chain Reaction, RNA, Messenger, biosynthesis, genetics
Subject categories Cancer and Oncology

Abstract

Polymorphous low-grade adenocarcinoma (PLGA) is a malignancy predominantly originating from the minor salivary glands. The molecular events underlying the pathogenesis of PLGA is poorly understood and no recurrent genetic aberrations have so far been identified. We used genome-wide, high-resolution aCGH analysis to explore genomic imbalances in 9 cases of PLGA. Because of the well-known morphologic similarities between PLGA and adenoid cystic carcinoma (ACC) we also analyzed all tumors for expression of the recently identified ACC-associated MYB-NFIB gene fusion. aCGH analysis revealed that the PLGA genome contains comparatively few copy number alterations (CNAs). Gains/losses of whole chromosomes or chromosome arms were more than twice as common as partial CNAs. Two cases showed gain of chromosome 8 and one case each gain of chromosome 9, loss of chromosome 22 and loss of the Y chromosome. One case showed loss of the entire 6q arm and one case an interstitial deletion of a 33-Mb segment within 6q22.1-q24.3. This region contains the MYB oncogene and the candidate tumor suppressor gene PLAGL1. RT-PCR analysis revealed that one of the 9 PLGAs expressed the ACC-associated MYB-NFIB gene fusion, illustrating the diagnostic difficulties associated with the diagnosis of these morphologically partly overlapping entities. Taken together, our findings indicate that the PLGA genome is genetically stable and contains comparatively few CNAs which is in line with the clinical observation that PLGA is a slow-growing, low-grade carcinoma with low metastatic potential.

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