Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Issue 10 (18th June 2014)

• Record Type: Journal Article
• Authors: Weinreb, Ilan; Zhang, Lei; Tirunagari, Laxmi MS; Sung, Yun‐Shao; Chen, Chun‐Liang; Perez‐Ordonez, Bayardo; Clarke, Blaise A; Skalova, Alena; Chiosea, Simion I; Seethala, Raja R; Waggott, Daryl; Boutros, Paul C; How, Christine; Liu, Fei‐Fei; Irish, Jonathan C; Goldstein, David P; Gilbert, Ralph; ud Din, Nasir; Assaad, Adel; Hornick, Jason L; Thompson, Lester DR; Antonescu, Cristina R
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 10(2014:Oct.)
• Page Start: 845
• Page End: 856
• Publication Date: 2014-06-18
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22195
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Polymorphous low‐grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low‐grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired‐end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs. Validated rearrangements were then screened by fluorescence in situ hybridization (FISH) in 60 cases. Histologic classification was performed without knowledge of fusion status and included: 21 CAMSG, 18 classic PLGA, and 21 with "mixed/indeterminate" features. The RNAseq of 2 CAMSGs showed <italic>ARID1A‐PRKD1</italic> and <italic>DDX3X‐PRKD1</italic> fusions, respectively, while no fusion candidates were identified in two PLGAs. FISH for <italic>PRKD1</italic> rearrangements identified 11 additional cases (22%), two more showing <italic>ARID1A‐PRKD1</italic> fusions. As <italic>PRKD2</italic> and <italic>PRKD3</italic> share similar functions with <italic>PRKD1</italic> in the diacylglycerol and protein kinase C signal transduction pathway, we expanded the investigation for these genes by FISH. Six additional cases each showed <italic>PRKD2</italic> and <italic>PRKD3</italic> rearrangements. Of the 26 (43%) fusion‐positive tumors, there were 16 (80%) CAMSGs and 9 (45%) indeterminate cases. A <italic>PRKD2</italic> rearrangement was detected in one PLGA (6%). We describe novel and recurrent gene rearrangements in <italic>PRKD1–3</italic> primarily in CAMSG, suggesting a possible pathogenetic dichotomy from "classic" PLGA. However, the presence of similar genetic findings in half of the indeterminate cases and a single PLGA suggests a possible shared pathogenesis for these tumor types. © 2014 Wiley Periodicals, Inc.</p> </abstract>