PMID- 24942367
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20201209
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 53
IP  - 10
DP  - 2014 Oct
TI  - Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma 
      of salivary gland origin.
PG  - 845-56
LID - 10.1002/gcc.22195 [doi]
AB  - 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 
      ARID1A-PRKD1 and DDX3X-PRKD1 fusions, respectively, while no fusion candidates 
      were identified in two PLGAs. FISH for PRKD1 rearrangements identified 11 
      additional cases (22%), two more showing ARID1A-PRKD1 fusions. As PRKD2 and PRKD3 
      share similar functions with PRKD1 in the diacylglycerol and protein kinase C 
      signal transduction pathway, we expanded the investigation for these genes by 
      FISH. Six additional cases each showed PRKD2 and PRKD3 rearrangements. Of the 26 
      (43%) fusion-positive tumors, there were 16 (80%) CAMSGs and 9 (45%) 
      indeterminate cases. A PRKD2 rearrangement was detected in one PLGA (6%). We 
      describe novel and recurrent gene rearrangements in PRKD1-3 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.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Weinreb, Ilan
AU  - Weinreb I
AD  - Department of Pathology, University Health Network, Toronto, ON, Canada; 
      Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON, Canada.
FAU - Zhang, Lei
AU  - Zhang L
FAU - Tirunagari, Laxmi M S
AU  - Tirunagari LM
FAU - Sung, Yun-Shao
AU  - Sung YS
FAU - Chen, Chun-Liang
AU  - Chen CL
FAU - Perez-Ordonez, Bayardo
AU  - Perez-Ordonez B
FAU - Clarke, Blaise A
AU  - Clarke BA
FAU - Skalova, Alena
AU  - Skalova A
FAU - Chiosea, Simion I
AU  - Chiosea SI
FAU - Seethala, Raja R
AU  - Seethala RR
FAU - Waggott, Daryl
AU  - Waggott D
FAU - Boutros, Paul C
AU  - Boutros PC
FAU - How, Christine
AU  - How C
FAU - Liu, Fei-Fei
AU  - Liu FF
FAU - Irish, Jonathan C
AU  - Irish JC
FAU - Goldstein, David P
AU  - Goldstein DP
FAU - Gilbert, Ralph
AU  - Gilbert R
FAU - Ud Din, Nasir
AU  - Ud Din N
FAU - Assaad, Adel
AU  - Assaad A
FAU - Hornick, Jason L
AU  - Hornick JL
FAU - Thompson, Lester D R
AU  - Thompson LD
FAU - Antonescu, Cristina R
AU  - Antonescu CR
LA  - eng
GR  - P01CA47179/CA/NCI NIH HHS/United States
GR  - P50 CA 140146-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140618
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (ARID1A protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.- (protein kinase D)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.1.- (DDX3X protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Adenocarcinoma/*genetics/metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Line
MH  - DEAD-box RNA Helicases/genetics/metabolism
MH  - DNA-Binding Proteins
MH  - Female
MH  - *Gene Fusion
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Nuclear Proteins/genetics/metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Protein Kinase C/*genetics/metabolism
MH  - Salivary Gland Neoplasms/*genetics/metabolism/pathology
MH  - Salivary Glands/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Young Adult
EDAT- 2014/06/20 06:00
MHDA- 2015/03/31 06:00
CRDT- 2014/06/20 06:00
PHST- 2014/03/13 00:00 [received]
PHST- 2014/05/29 00:00 [accepted]
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - 10.1002/gcc.22195 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2014 Oct;53(10):845-56. doi: 10.1002/gcc.22195. Epub 
      2014 Jun 18.