1. Adenoid cystic carcinoma of the Bartholin's gland is underpinned by MYB- and MYBL1- rearrangements.
- Author
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Feinberg, Jacqueline, Da Cruz Paula, Arnaud, da Silva, Edaise M., Pareja, Fresia, Patel, Juber, Zhu, Yingjie, Selenica, Pier, Leitao, Mario M., Abu-Rustum, Nadeem R., Reis-Filho, Jorge S., Joehlin-Price, Amy, and Weigelt, Britta
- Subjects
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BARTHOLIN'S gland , *ADENOID cystic carcinoma , *PROTEIN overexpression , *GENE fusion , *GENE rearrangement , *SOMATIC mutation - Abstract
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. 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. 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. 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. • Adenoid cystic carcinoma of the Bartholin's gland (AdCC-BG) is underpinned by MYB or MYBL1 fusion genes. • AdCC-BGs have few somatic genetic alterations in addition to the MYB/ MYBL1 fusion gene. • AdCC-BG constitutes a genotypic–phenotypic correlation. • MYB/ MYBL1 rearrangement assessment may be used as an ancillary marker for AdCC-BG diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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