High prevalence of TERT promoter mutations in micropapillary urothelial carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Doreen Nguyen, Diana Taheri, Simeon Springer, Morgan Cowan, Gunes Guner, Maria Angelica Mendoza Rodriguez, Yuxuan Wang, Isaac Kinde, Christopher J. VandenBussche, Matthew T. Olson, Bernardo F. P. Ricardo, Isabela Cunha, Kazutoshi Fujita, Dilek Ertoy, Kenneth W. Kinzler, Trinity J. Bivalacqua, Nickolas Papadopoulos, Bert Vogelstein, George J. Netto

ABSTRACT

Somatic activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Little is known, however, about TERT-mutation status in the relatively uncommon but clinically aggressive micropapillary (MPC) variant. We evaluated the presence of TERT promoter mutations in MPC of the bladder and upper urinary tract. A retrospective search of our archives for MPC and UC with micropapillary features (2005-2014) was performed. All slides were reviewed to confirm the histologic diagnosis. Thirty-three specimens from 31 patients had FFPE blocks available for DNA analysis and were included in the study. Intratumoral areas of non-micropapillary histology were also evaluated when present. Samples were analyzed with Safe-SeqS, a sequencing error reduction technology, and sequenced using the Illumina MiSeq platform. TERT promoter mutations were detected in all specimens with pure MPC (18 of 18) and UC with focal micropapillary features (15 of 15). Similar to conventional UC, the predominant mutations identified occurred at positions -124 (C228T) (85 %) and -146 (C250T) (12 %) bp upstream of the TERT ATG start site. In heterogeneous tumors with focal variant histology, intratumoral concordant mutations were found in variant (MPC and non-MPC) and corresponding conventional UC. We found TERT promoter mutations, commonly found in conventional UC, to be frequently present in MPC. Our finding of concordant intratumoral mutational alterations in cases with focal variant histology lends support to the common oncogenesis origin of UC and its variant histology. More... »

PAGES

427-434

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00428-016-2001-2

DOI

http://dx.doi.org/10.1007/s00428-016-2001-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004952378

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27520411


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