Absence of Promoter Mutation in TBC1D12 Gene in Solid and Hematologic Neoplasia

[摘要] TBC1 domain family member 12 (TBC1D12) gene encodes a recycling endosome-resident protein that binds with Rab11 [1]. Neither cancer-related functions nor biologic functions of TBC1D12 are largely unknown currently. Recently, Rheinbay et al. analyzed genome-wide somatic mutations in promoters in breast cancers and identified the promoter mutations in several genes [2]. One of the top-ranked genes with the promoter mutations was TBC1D12 (3.9% of breast cancers), the mutations of which decreased TBC1D12 expression, suggesting their loss-of-function activities [2]. Of note, the promoter mutations of TBC1D12 were found recurrently at two hotspot sites (chr10: 96162368 and 96,162,370). Promoter alterations such as somatic mutation and aberrant methylation in tumor suppressor genes, oncogenes, transcription factors and drug response genes are known to play a role in the cancer pathogenesis [3]. Together, these data suggest a possibility that promoter mutation of TBC1D12 gene might be present not only in breast cancer but also in other cancers and play a role in cancer development. For this, tumor tissues from 2018 Korean patients, including hematologic, epithelial and mesenchymal tumor from various origins, were analyzed in this study (Table 1). For solid tumors, malignant and normal cells were selectively procured from by microdissection [4]. Because TBC1D12 promoter mutations have been focused in a narrow region (chromosome 10: 96162368–6,162,370) [2], we amplified this region with a primer pair by polymerase chain reaction (PCR) (forward: 5- CAGCACCCAGAGCTGTTCTC-3, reverse: 5- GCCCGGATTACCTTCCTGTC-3) and subsequently analyzed by single-strand conformation polymorphism (SSCP) and DNA sequencing. Other procedures of the PCR-SSCP were described in our previous studies [4].