A novel cytogenetic and molecular characterization of renal metanephric adenoma: Identification of partner genes involved in translocation t(9;15)(p24;q24)

作者：Catic Aida; Kurtovic Kozaric Amina; Johnson Sarah H; Vasmatzis George; Pins Michael R; Kogan Jillene^*

来源：Cancer Genetics, 2017, 214: 9-15.

DOI：10.1016/j.cancergen.2017.03.001

• Metanephric adenoma
• Cytogenetics
• Chromosomal translocations
• KANK1-NTRK3
• Renal cell carcinoma

Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized. Recent data suggest that 90% of MA have BRAF(V600E) mutations; the genetics of the remaining 10% are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported. However, the potential role of the KANK1 gene, which lies near the breakpoint of the short arm of chromosome 9p24, in the etiology of MA was not examined. We identified the same cytogenetic aberration utilizing molecular cytogenetic techniques in a 22-year-old female patient, and further investigated the genes involved in the translocation that might have contributed to tumorigenesis. A series of fluorescence in situ hybridization (FISH) probes identified the rearranged genes to be KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Mate-Pair genome sequencing validated the balanced translocation between 9p24.3 and 15q25.3, involving genes KANK1 and NTRK3, respectively. BRAP(V600E) mutational analysis was normal. Our findings indicate that gene fusions may be one mechanism by which functionally relevant genes are altered in the development of MA. Molecular and cytogenetic analyses have elucidated a novel genetic aberration, which helps to provide a better understanding of this genomic change and assist in diagnosis and classification of new subgroups/entities in metanephric adenomas.

• 出版日期2017-8