Promoter Mutation Analysis of ALDOA Gene in Solid Tumors and Acute Leukemias

[摘要] Alteration in the cellular metabolism is one of the cancer hallmarks. Fructose-1,6-bisphosphate aldolase A (ALDOA) gene encodes an enzyme ALDOA that converts fructose 1,6-bisphosphate into G3P and DHAP, which in glycolysis have proven benefits for cancer cells [1]. High ALDOA expression has been demonstrated in many cancers and is associated with overall survival of the patients, suggesting its functions as a candidate oncogene [2]. However, genetic alterations of ALDOA in the coding sequences are reported to be rare. A recent genome-wide sequecning study for promoters in breast cancers discovered somatic promoter mutations in many genes, including ALDOA (3.3% of breast cancers) [3]. The ALDOA promoter mutation was found at a hotspot (chr16: 30077131). It is wellknown that alterations in promoter play a role in the cancer pathogenesis [4], suggesting that ALDOA promoter mutation might reside in other cancers as well as in breast cancer. In this study, human tumor tissues from 1834 patients from diverse organs were analyzed (Table 1). Approval for this study was obtained from the Catholic University of Korea, College of Medicine’s institutional review board. Since the ALDOA promoter mutation has been found in the hotspot [3], we amplified a region encompassing the hotspot with a primer pair by polymerase chain reaction (PCR) (forward: 5-TCGTAAAG GAAAAAGCTCGGC -3, reve rse: 5 -GATTCAAG GAGAGAACGCGG-3, size: 174 bps) and subsequently displayed in single-strand conformation polymorphism (SSCP) and DNA sequencing [5].