BRD4-NUT Fusion Oncogene Analysis by RT-PCR in Sinonasal Undifferentiated Carcinoma (SNUC) and Other Aggressive Primary Sinonasal Malignancies: A Study of 15 Cases
JJ Garcia, K Nafa, DL Carlson, EL Barnes, RR Seethala, M Ladanyi. University of Pittsburgh, Pittsburgh, PA; Memorial Sloan-Kettering Cancer Center, New York City, NY
Background: NUT-rearranged carcinomas (NRCs), also termed NUT midline carcinomas (NMCs), have been characterized as poorly differentiated carcinomas of midline anatomic location that affect young patients and invariably follow a lethal clinical course. Although the most common balanced chromosomal translocation is represented by a t(15;19) causing a BRD4-NUT fusion, other fusion variants involving NUT and other partners have been observedthe so-called NUT-variant carcinomas. Recently, NUT rearrangements have been identified using fluorescent in-situ hybridization (FISH) in a subset of undifferentiated carcinomas of the sinonasal tract in older patients. This study employed reverse-transcription polymerase chain reaction (RT-PCR) to evaluate the incidence of the BRD4-NUT oncogene in sinonasal undifferentiated carcinomas (SNUCs) and other primary sinonasal malignancies.
Design: We carried out RT-PCR for the detection of the BRD4-NUT translocation in 15 cases of primary sinonasal malignancy. Eight of the 15 cases were classified as SNUCs by morphology and immunophenotype. The remaining cases studied were diagnosed as poorly differentiated carcinoma (3), squamous cell carcinoma (3), and lymphoepithelial carcinoma (1). The patients were predominantly older adults (median age, 61.3 years) and there were 8 men and 7 women. Each sample was evaluated twice with different primer sets (BR2276F/NUT1194R and BR2334F/NUT1132R). Two previously reported cell lines from t(15;19) carcinomas served as positive controls.
Results: RT-PCR studies revealed no BRD4-NUT fusion products with either primer set in any of the cases evaluated (0/15). BRD4-NUT fusion products were reproducibly obtained with both primer sets in the positive controls whereas no such products were obtained in the negative controls.
Conclusions: Our evaluation by RT-PCR of eight SNUCs showed none to have a BRD4-NUT fusion oncogene. Our results suggest that BRD4-NUT fusions are uncommon in SNUCs but our RT-PCR-based approach cannot exclude the possibility of variant NUT rearrangements in some cases of SNUC. Previously reported sinonasal tumors with NUT rearrangement are likely NUT-variant carcinomas that are more amenable to detection by FISH.
Category: Head & Neck
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 170, Monday Morning