PMID- 38368814
OWN - NLM
STAT- Publisher
LR  - 20240218
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 185
DP  - 2024 Feb 17
TI  - Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and 
      MYBL1- rearrangements.
PG  - 58-67
LID - S0090-8258(24)00112-4 [pii]
LID - 10.1016/j.ygyno.2024.02.015 [doi]
AB  - OBJECTIVE: Adenoid cystic carcinoma (AdCC) of the Bartholin's gland (AdCC-BG) is 
      a very rare gynecologic vulvar malignancy. AdCC-BGs are slow-growing but locally 
      aggressive and are associated with high recurrence rates. Here we sought to 
      characterize the molecular underpinning of AdCC-BGs. METHODS: AdCC-BGs (n = 6) 
      were subjected to a combination of RNA-sequencing, targeted DNA-sequencing, 
      reverse-transcription PCR, fluorescence in situ hybridization (FISH) and MYB 
      immunohistochemistry (IHC). Clinicopathologic variables, somatic mutations, copy 
      number alterations and chimeric transcripts were assessed. RESULTS: All six 
      AdCC-BGs were biphasic, composed of ductal and myoepithelial cells. Akin to 
      salivary gland and breast AdCCs, three AdCC-BGs had the MYB::NFIB fusion gene 
      with varying breakpoints, all of which were associated with MYB overexpression by 
      IHC. Two AdCC-BGs were underpinned by MYBL1 fusion genes with different gene 
      partners, including MYBL1::RAD51B and MYBL1::EWSR1 gene fusions, and showed MYB 
      protein expression. Although the final AdCC-BG studied had MYB protein 
      overexpression, no gene fusion was identified. AdCC-BGs harbored few additional 
      somatic genetic alterations, and only few mutations in cancer-related genes were 
      identified, including GNAQ, GNAS, KDM6A, AKT1 and BCL2, none of which were 
      recurrent. Two AdCC-BGs, both with a MYB::NFIB fusion gene, developed metastatic 
      disease. CONCLUSIONS: AdCC-BGs constitute a convergent phenotype, whereby 
      activation of MYB or MYBL1 can be driven by the MYB::NFIB fusion gene or MYBL1 
      rearrangements. Our observations further support the notion that AdCCs, 
      irrespective of organ site, constitute a genotypic-phenotypic correlation. 
      Assessment of MYB or MYBL1 rearrangements may be used as an ancillary marker for 
      the diagnosis of AdCC-BGs.
CI  - Copyright (c) 2024 Elsevier Inc. All rights reserved.
FAU - Feinberg, Jacqueline
AU  - Feinberg J
AD  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Da Cruz Paula, Arnaud
AU  - Da Cruz Paula A
AD  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - da Silva, Edaise M
AU  - da Silva EM
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Pareja, Fresia
AU  - Pareja F
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Patel, Juber
AU  - Patel J
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Zhu, Yingjie
AU  - Zhu Y
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Selenica, Pier
AU  - Selenica P
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Leitao, Mario M Jr
AU  - Leitao MM Jr
AD  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Abu-Rustum, Nadeem R
AU  - Abu-Rustum NR
AD  - Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Reis-Filho, Jorge S
AU  - Reis-Filho JS
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Joehlin-Price, Amy
AU  - Joehlin-Price A
AD  - Cleveland Clinic Pathology and Laboratory Medicine Institute, Cleveland, OH, USA.
FAU - Weigelt, Britta
AU  - Weigelt B
AD  - Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA. Electronic address: weigeltb@mskcc.org.
LA  - eng
PT  - Journal Article
DEP - 20240217
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
SB  - IM
OTO - NOTNLM
OT  - Adenoid cystic carcinoma
OT  - Bartholin's glands
OT  - MYB
OT  - MYB::NFIB fusion gene
OT  - MYBL1
COIS- Declaration of competing interest B. Weigelt reports research funding from REPARE 
      Therapeutics, outside the submitted work. F. Pareja is a member of the scientific 
      advisory board of MultiplexDx Inc. J.S. Reis-Filho reported receiving 
      personal/consultancy fees from Goldman Sachs, Bain Capital, REPARE Therapeutics, 
      Saga Diagnostics and Paige.AI, membership of the scientific advisory boards of 
      VolitionRx, REPARE Therapeutics and Paige.AI, membership of the Board of 
      Directors of Grupo Oncoclinicas, and ad hoc membership of the scientific advisory 
      boards of AstraZeneca, Merck, Daiichi Sankyo, Roche Tissue Diagnostics and 
      Personalis, outside the submitted work. M. Leitao reports personal fees from 
      Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. N.R. Abu-Rustum 
      reports research funding paid to the institution from GRAIL; Memorial Sloan 
      Kettering Cancer Center also has equity in GRAIL. The remaining authors have no 
      competing interests to disclose.
EDAT- 2024/02/19 00:42
MHDA- 2024/02/19 00:42
CRDT- 2024/02/18 18:10
PHST- 2024/01/13 00:00 [received]
PHST- 2024/02/09 00:00 [accepted]
PHST- 2024/02/19 00:42 [medline]
PHST- 2024/02/19 00:42 [pubmed]
PHST- 2024/02/18 18:10 [entrez]
AID - S0090-8258(24)00112-4 [pii]
AID - 10.1016/j.ygyno.2024.02.015 [doi]
PST - aheadofprint
SO  - Gynecol Oncol. 2024 Feb 17;185:58-67. doi: 10.1016/j.ygyno.2024.02.015.