Loss of LPL, del(8p22)
Lipoprotein lipase (LPL) gene located at 8p22 region and c-myc gene located at the 8q24 region, allows for prognosis in prostate cancer. Two of the most significant genetic alterations detected in prostate cancer include 8q24 gain and loss 8p21-22 heterozygous. It has been found that deletion of LPL locus is observed in 68% of analyzed prostate cancers by FISH analysis.
Gain of 8q24, a common genetic alteration in prostate cancer, is is often accompanied by loss of 8p21-22. Some studies suggest that the loss of 8p22 is associated with a poor prognosis. It has further been reported that chromosomal region 8p23.1-8p21.1 may harbor one or more important prostate cancer susceptible loci based on linkage analyses in 159 hereditary prostate cancer families. Thus, cancer-susceptible genes mapped close to the LPL gene could be affected by LPL deletion, and exert combined effects in promoting carcinogenesis.
Moreover, an LPL Ser447stop polymorphism has been shown to be associated with prostate cancer risk and the LPL gene is commonly methylated in prostate tumors. LPL promoter CpG island methylation has been revealed in 45% of LPL-deleted tumors and in 22% of LPL-retaining tumors. Biallelic inactivation of LPL by chromosomal deletion and promoter methylation may thus contribute to prostate tumorigenesis, but information is lacking regarding pancreatic cancer.
References
- Takasu, S et al. (2012) Biochem Res Int. 2012:398697
- Gallucci, M et al. (2009) Urol Oncol. 27(5):502-8.
- J. W. Kim, et al. (2009) International Journal of Cancer, 124(3): 734–738.
- Gallucci, M et al. (2006) Cancer Letters. 237(1):76–82.
