Deep intronic point mutations of the KIT gene in a female patient with cutaneous clear cell sarcoma and her family

• Published in: Cancer genetics Vol. 205; no. 4; pp. 182 - 185
• Main Authors: Gambichler, Thilo, Pantelaki, Ioanna, Othlinghaus, Nick, Moritz, Rose K.C, Stricker, Ingo, Skrygan, Marina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2012
• Subjects: Activating Transcription Factor 1 - genetics; Adolescent; Calmodulin-Binding Proteins - genetics; Clear cell sarcoma; Clear cells; EWSR1-ATF1 chimeric gene; Female; Gene Fusion; Germ-Line Mutation; Hematology, Oncology and Palliative Medicine; Humans; intronic point mutation; Introns; KIT gene; Male; malignant melanoma of soft parts; Medical Education; Oncogene Proteins, Fusion - genetics; Point Mutation; RNA-Binding Protein EWS; RNA-Binding Proteins - genetics; Sarcoma, Clear Cell - genetics; Sarcoma, Clear Cell - pathology; Skin Neoplasms - genetics; Skin Neoplasms - pathology; EWSR1-ATF1 chimeric gene; Clear cell sarcoma; malignant melanoma of soft parts; intronic point mutation; KIT gene
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2012.02.001

Clear cell sarcoma (CCS) of tendons and aponeuroses is an aggressive neoplasm that is characterized by a pathognomonic translocation, t(12;22)(q13;q12), resulting in an EWSR1-ATF1 chimeric gene. We report for the first time a female patient with CCS exhibiting both EWSR1-ATF1 fusion transcripts and hereditary homozygous point mutations in introns 11 and 16 of the KIT gene. Her parents and two brothers each had heterozygous point mutations in intron 11 or intron 16 of the KIT gene. The functional significance of these germline deep intronic point mutations and their relationship to the pathogenesis of CCS are unclear. Future studies investigating KIT intron mutations in a larger cohort of CCS patients are warranted.