Midline Carcinoma of Children and Young Adults With NUT Rearrangement

• Published in: Journal of clinical oncology Vol. 22; no. 20; pp. 4135 - 4139
• Main Authors: FRENCH, Christopher A, KUTOK, Jeffery L, MIYOSHI, Isao, PEREZ-ATAYDE, Antonio R, ASTER, Ion C, FLETCHER, Jonathan A, FAQUIN, William C, TORETSKY, Jeffrey A, ANTONESCU, Cristina R, GRIFFIN, Constance A, NOSE, Vania, VARGAS, Sara O, MOSCHOVI, Mary, TZORTZATOU-STATHOPOULOU, Fotini
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15.10.2004; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Antigens, CD34 - analysis; Biological and medical sciences; Carcinoma, Squamous Cell; Child; Child, Preschool; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 19; Female; Humans; In Situ Hybridization, Fluorescence; Infant; Infant, Newborn; Male; Medical sciences; Middle Aged; Neoplasms - genetics; Nuclear Proteins; Oncogene Proteins, Fusion - analysis; Oncogene Proteins, Fusion - genetics; Survival Rate; Transcription Factors; Translocation, Genetic; Tumors; Human; Cancerology; Carcinoma; Nuts; Young adult; Gene rearrangement; Malignant tumor; Child
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.02.107

A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features. Carcinomas (N = 98) in young individuals (median age, 32.5 years) were screened for NUT and BRD4 rearrangements using dual-color fluorescence in situ hybridization. Four published carcinomas with BRD4 and NUT rearrangements were also evaluated. Immunophenotypic analyses were performed. Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. All NUT-rearranged carcinomas (NRCs) arose from midline epithelial structures, including the first example arising below the diaphragm. Patients were young (median age, 17.6 years). Squamous differentiation (seen in 82% of NRCs) was particularly striking in NUT-variant cases. In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of 45 NUT wild-type carcinomas. NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and, therefore, holds promise as a diagnostic test for this distinctive clinicopathologic entity.