PMID- 37595638
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20231124
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 36
IP  - 11
DP  - 2023 Nov
TI  - Comprehensive Molecular Characterization of Polymorphous Adenocarcinoma, 
      Cribriform Subtype: Identifying Novel Fusions and Fusion Partners.
PG  - 100305
LID - S0893-3952(23)00210-7 [pii]
LID - 10.1016/j.modpat.2023.100305 [doi]
AB  - Polymorphous adenocarcinoma (PAC) is a common, usually low-grade salivary gland 
      carcinoma. While conventional PACs are most associated with PRKD1 p.E710D hotspot 
      mutations, the cribriform subtype is often associated with gene fusions in PRKD1, 
      PRKD2, or PRKD3. These fusions have been primarily identified by fluorescence in 
      situ hybridization (FISH) analysis, with a minority evaluated by next-generation 
      sequencing (NGS). Many of the reported fusions were detected by break-apart FISH 
      probes and therefore have unknown partners or were negative by FISH altogether. 
      In this study, we aimed to further characterize the fusions associated with PAC 
      with NGS. Fifty-four PACs (exclusively cribriform and mixed/intermediate types to 
      enrich the study for fusion-positive cases) were identified and subjected to NGS. 
      Fifty-one cases were successfully sequenced, 28 of which demonstrated gene 
      fusions involving PRKD1, PRKD2, or PRKD3. There were 10 cases with the PRKD1 
      p.E710D mutation. We identified a diverse group of fusion partners, including 13 
      novel partners, 3 of which were recurrent. The most common partners for the PRKD 
      genes were ARID1A and ARID1B. The wide variety of involved genes is unlike in 
      other salivary gland malignancies and warrants a broader strategy of sequencing 
      for molecular confirmation for particularly challenging cases, as our NGS study 
      shows.
CI  - Copyright (c) 2023 United States & Canadian Academy of Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Hahn, Elan
AU  - Hahn E
AD  - Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, 
      Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University 
      of Toronto, Ontario, Canada. Electronic address: elan.hahn@sinaihealth.ca.
FAU - Xu, Bin
AU  - Xu B
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Katabi, Nora
AU  - Katabi N
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Dogan, Snjezana
AU  - Dogan S
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Smith, Stephen M
AU  - Smith SM
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Ontario, Canada; Laboratory Medicine Program, University Health Network, Toronto 
      General Hospital, Toronto, Ontario, Canada.
FAU - Perez-Ordonez, Bayardo
AU  - Perez-Ordonez B
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Ontario, Canada; Laboratory Medicine Program, University Health Network, Toronto 
      General Hospital, Toronto, Ontario, Canada.
FAU - Patel, Paras B
AU  - Patel PB
AD  - ProPath, Dallas, Texas.
FAU - MacMillan, Christina
AU  - MacMillan C
AD  - Department of Pathology and Laboratory Medicine, Sinai Health System, Toronto, 
      Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University 
      of Toronto, Ontario, Canada.
FAU - Lubin, Daniel J
AU  - Lubin DJ
AD  - Department of Pathology and Laboratory Medicine, Emory University Hospital, 
      Atlanta, Georgia.
FAU - Gagan, Jeffrey
AU  - Gagan J
AD  - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 
      Texas.
FAU - Weinreb, Ilan
AU  - Weinreb I
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Ontario, Canada; Laboratory Medicine Program, University Health Network, Toronto 
      General Hospital, Toronto, Ontario, Canada.
FAU - Bishop, Justin A
AU  - Bishop JA
AD  - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 
      Texas.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230817
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
SB  - IM
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Adenocarcinoma/genetics/pathology
MH  - *Salivary Gland Neoplasms/genetics/pathology
MH  - Mutation
MH  - Gene Fusion
OTO - NOTNLM
OT  - PRKD
OT  - cribriform
OT  - gene fusions
OT  - head and neck pathology
OT  - molecular pathology
OT  - polymorphous adenocarcinoma
OT  - salivary gland tumors
EDAT- 2023/08/19 11:42
MHDA- 2023/11/20 06:55
CRDT- 2023/08/18 19:22
PHST- 2023/04/24 00:00 [received]
PHST- 2023/07/12 00:00 [revised]
PHST- 2023/08/07 00:00 [accepted]
PHST- 2023/11/20 06:55 [medline]
PHST- 2023/08/19 11:42 [pubmed]
PHST- 2023/08/18 19:22 [entrez]
AID - S0893-3952(23)00210-7 [pii]
AID - 10.1016/j.modpat.2023.100305 [doi]
PST - ppublish
SO  - Mod Pathol. 2023 Nov;36(11):100305. doi: 10.1016/j.modpat.2023.100305. Epub 2023 
      Aug 17.