Genetic variations of the midkine (MK) gene in human sporadic colorectal and gastric cancers

Midkine (MK), a retinoic acid responsible protein, is regulated during deve lopment and may play an important role in tumorigenesis. A search for genet ic variations of the MK gene, located on chromosome 11q11.2 in humans, has not yet been conducted in cancers. To examine the entire coding region, as well as 4 regions of the promoter covering all functional motifs, 8 sets of intron-based and promoter region primers were designed. Using these primer s, polymerase chain reaction-single strand conformation polymorphism (PCR-S SCP) analysis of genomic DNA samples from 60 sporadic colorectal and 37 spo radic gastric cancer patients was carried out. This analysis, followed by D NA sequencing, revealed a heterozygous g/t polymorphism at the 62nd base on intron 3 in five colorectal tumors (8.3%) and one gastric tumor (2.7%). In the promoter region, a heterozygous CTT deletion, creating a (CTTTT)(2) re peat, in one colorectal cancer sample (1.67%) and a heterozygous 2-bp delet ion in the G(7) tract in another colorectal cancer patient were detected. A /C and A/A alleles were also detected at nt. -1741 in 36 (97.3%) and one (2 .7%) gastric cancer samples, respectively. The A/G alleles were observed in all colorectal cancer patients (100%). All variations observed in the prom oter region showed polymorphism. These results suggest that in sporadic col orectal and gastric cancers some gene alterations are present in the MK pro moter region, but alterations in the coding region are rare.