Synapse - Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements

Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements Journal Article

Authors:	Feinberg, J.; Da Cruz Paula, A.; da Silva, E. M.; Pareja, F.; Patel, J.; Zhu, Y.; Selenica, P.; Leitao, M. M. Jr; Abu-Rustum, N. R.; Reis-Filho, J. S.; Joehlin-Price, A.; Weigelt, B.
Article Title:	Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements
Abstract:	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. © 2024 Elsevier Inc.
Keywords:	adenoid cystic carcinoma; myb; mybl1; bartholin's glands; myb::nfib fusion gene
Journal Title:	Gynecologic Oncology
Volume:	185
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2024-06-01
Start Page:	58
End Page:	67
Language:	English
DOI:	10.1016/j.ygyno.2024.02.015
PUBMED:	38368814
PROVIDER:	scopus
PMCID:	PMC11179993
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185605370&doi=10.1016%2fj.ygyno.2024.02.015&partnerID=40&md5=dc2c223242d21b7acc66d4429e048c84
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Britta Weigelt -- Source: Scopus