Unexpected information of DNA deletions in genome: analysis of one VHL case with Array-CGH

作者：Yang, Yang; Ji, Changwei; Zhu, Xiangyu; Chen, Huimei^*; Guo, Hongqian^*

来源：International Journal of Clinical and Experimental Medicine, 2016, 9(4): 7175-7183.

• Von Hippel-Lindau
• array comparative genomic hybridization
• coding deletion
• alu element

Background: Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome that occurs as a consequence of an inactivation of the VHL gene. Point mutations in VHL are a major cause for VHL disease, and fragment deletions contribute to similar to 30% of VHL patients. Array Comparative Genomic Hybridization (Array-CGH) is a powerful tool for the identification of genomic deletions, and often reveals unexpected information as a non-targeted method. Method: We extracted the DNA from the patients' blood and screened for point mutations in VHL by PCR and large deletions by Array Comparative Genomic Hybridization (Array-CGH). Real-time quantitative PCR was used to confirm the deletion of VHL gene and expression of VHL in tumor tissue. Results: We present a family case of VHL syndrome, showing hemangioblastomas in the central nervous system and retina, multiple pancreatic cysts and clear-cell renal cell carcinoma. After excluding point mutations in VHL gene exons and conjunctive regions, we identified a similar to 9 kb deletion of chromosome 3p25.3 with Array-CGH analysis. Real-time PCR confirmed a heterozygous deletion in exon 3 of the VHL gene. Additional 90 DNA deletions were detected ranging from 5 kb to 160 kb in size. Moreover, 70.3% of the breakpoints were located in Alu elements. Conclusions: This study confirmed that DNA deletions contribute to familial VHL disease. It also highlights that coding deletions appear to be more frequent than expected, and that Alu-mediated recombination is the major mechanism.

• 出版日期2016
• 单位南京大学