Primary tracheobronchial adenoid cystic carcinoma is rare, accounting for less than 1% of all lung tumors. Many adenoid cystic carcinomas have been reported to have a specific chromosome translocation t(6;9)/MYB-NFIB. More recently, t(8;9)/MYBL1-NFIB gene fusion was reported in salivary gland adenoid cystic carcinomas which lacked a t(6;9)/MYB-NFIB. Two prior studies showed t(6;9)/MYB-NFIB in tracheobronchial adenoid cystic carcinoma; however, only rare cases of MYBL1 rearrangement have been reported in this carcinoma. In this study, we used targeted RNA sequencing to investigate fusion genes in tracheobronchial adenoid cystic carcinoma at our institution. Fusions of either MYB or MYBL1 genes were detected in 7 of 7 carcinomas. Three cases had MYB-NFIB, and 3 had MYBL1-NFIB. The remaining case showed a rare MYBL1-RAD51B fusion. These findings suggest that rearrangement involving MYB or MYBL1 is a hallmark of tracheobronchial adenoid cystic carcinoma.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $52.67 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Zhu F, Liu Z, Hou Y, He D, Ge X, Bai C, et al. Primary salivary gland-type lung cancer: clinicopathological analysis of 88 cases from China. J Thorac Oncol. 2013;8:1578–84.
Molina JR, Aubry MC, Lewis JE, Wampfler JA, Williams BA, Midthun DE, et al. Primary salivary gland-type lung cancer: spectrum of clinical presentation, histopathologic and prognostic factors. Cancer. 2007;110:2253–9.
Falk N, Weissferdt A, Kalhor N, Moran CA. Primary pulmonary salivary gland-type tumors: a review and update. Adv Anat Pathol. 2016;23:13–23.
Ishikawa Y, Dacic S, Nicholson AG. Adenoid cystic carcinoma. In: Travis WD, Brambilla E, Burke A, Marx A, Nicholson AG (eds.). WHO Classification of tumours of the lung, pleura, thymus and heart. International Agency for Research on Cancer: Lyon, 2015;101–2.
Roden AC, Greipp PT, Knutson DL, Kloft-Nelson SM, Jenkins SM, Marks RS, et al. Histopathologic and cytogenetic features of pulmonary adenoid cystic carcinoma. J Thorac Oncol. 2015;10:1570–5.
Stephens PJ, Davies HR, Mitani Y, Van Loo P, Shlien A, Tarpey PS, et al. Whole exome sequencing of adenoid cystic carcinoma. J Clin Invest. 2013;123:2965–8.
Ho AS, Kannan K, Roy DM, Morris LG, Ganly I, Katabi N, et al. The mutational landscape of adenoid cystic carcinoma. Nat Genet. 2013;45:791–8.
Mitani Y, Liu B, Rao PH, Borra VJ, Zafereo M, Weber RS, et al. Novel MYBL1 gene rearrangements with recurrent MYBL1-NFIB fusions in salivary adenoid cystic carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2016;22:725–33.
Persson M, Andren Y, Mark J, Horlings HM, Persson F, Stenman G. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc Natl Acad Sci USA. 2009;106:18740–4.
Mitani Y, Li J, Rao PH, Zhao YJ, Bell D, Lippman SM, et al. Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: incidence, variability, and clinicopathologic significance. Clin Cancer Res. 2010;16:4722–31.
D’Alfonso TM, Mosquera JM, MacDonald TY, Padilla J, Liu YF, Rubin MA, et al. MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Hum Pathol. 2014;45:2270–80.
West RB, Kong C, Clarke N, Gilks T, Lipsick JS, Cao H, et al. MYB expression and translocation in adenoid cystic carcinomas and other salivary gland tumors with clinicopathologic correlation. Am J Surg Pathol. 2011;35:92–9.
Wetterskog D, Lopez-Garcia MA, Lambros MB, A’Hern R, Geyer FC, Milanezi F, et al. Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers. J Pathol. 2012;226:84–96.
Almeida-Pinto YD, Costa S, Andrade BAB, Altemani A, Vargas PA, Abreu LG, et al. t(6;9)(MYB-NFIB) in head and neck adenoid cystic carcinoma: A systematic review with meta-analysis. Oral Dis. 2018. https://doi.org/10.1111/odi.12984.
Martelotto LG, De Filippo MR, Ng CK, Natrajan R, Fuhrmann L, Cyrta J, et al. Genomic landscape of adenoid cystic carcinoma of the breast. J Pathol. 2015;237:179–89.
von Holstein SL, Fehr A, Persson M, Therkildsen MH, Prause JU, Heegaard S, et al. Adenoid cystic carcinoma of the lacrimal gland: MYB gene activation, genomic imbalances, and clinical characteristics. Ophthalmology. 2013;120:2130–8.
Fehr A, Kovacs A, Loning T, Frierson H Jr., van den Oord J, Stenman G. The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma. J Pathol. 2011;224:322–7.
North JP, McCalmont TH, Fehr A, van Zante A, Stenman G, LeBoit PE. Detection of MYB alterations and other immunohistochemical markers in primary cutaneous adenoid cystic carcinoma. Am J Surg Pathol. 2015;39:1347–56.
Wysocki PT, Izumchenko E, Meir J, Ha PK, Sidransky D, Brait M. Adenoid cystic carcinoma: emerging role of translocations and gene fusions. Oncotarget. 2016;7:66239–54.
Brayer KJ, Frerich CA, Kang H, Ness SA. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 2016;6:176–87.
Brill LB 2nd, Kanner WA, Fehr A, Andren Y, Moskaluk CA, et al. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011;24:1169–76.
Togashi Y, Dobashi A, Sakata S, Sato Y, Baba S, Seto A, et al. MYB and MYBL1 in adenoid cystic carcinoma: diversity in the mode of genomic rearrangement and transcripts. Mod Pathol. 2018;31:934–46.
Pei J, Cooper H, Flieder DB, Talarchek JN, Al-Saleem T, Uzzo RG, et al. NEAT1-TFE3 and KAT6A-TFE3 renal cell carcinomas, new members of MiT family translocation renal cell carcinoma. Mod Pathol. 2019. https://doi.org/10.1038/s41379-018-0191-7.
Xu B, Drill E, Ho A, Ho A, Dunn L, Prieto-Granada CN, et al. Predictors of outcome in adenoid cystic carcinoma of salivary glands: a clinicopathologic study with correlation between MYB fusion and protein expression. Am J Surg Pathol. 2017;41:1422–32.
George OL, Ness SA. Situational awareness: regulation of the myb transcription factor in differentiation, the cell cycle and oncogenesis. Cancers. 2014;6:2049–71.
Fujii K, Murase T, Beppu S, Saida K, Takino H, Masaki A, et al. MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma. Histopathology. 2017;71:823–34.
Gao R, Cao C, Zhang M, Lopez MC, Yan Y, Chen Z, et al. A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets. Oncotarget. 2014;5:12528–42.
Andersson MK, Afshari MK, Andren Y, Wick MJ, Stenman G. Targeting the oncogenic transcriptional regulator MYB in adenoid 307 cystic carcinoma by inhibition of IGF1R/AKT signaling. J Natl Cancer Inst. 2017;109. https://doi.org/10.1093/jnci/djx017.
This work is supported by NCI grant P30 CA006927.