CKS1B/CDKN2C (P18) Amplification/Deletion LPH 039 - Detail

Structural abnormalities of chromosome 1 are frequently detected in multiple myeloma, and have been correlated with more advanced disease¹.

Amplification of 1q21 (CKS1B) is one of the most recurrent chromosomal aberrations in multiple myeloma. Over-expression of the CKS1B gene up-regulates cell cycle progression resulting in a more proliferative disease². This is related to the advanced phenotype of multiple myeloma and therefore may be associated with poor prognosis and disease progression^3,4. Gain of 1q21 has been linked to inferior survival and further amplification is observed in disease relapse. In has been shown that gain of 1q21 copy number is not an independent prognostic factor in multiple myeloma and is often associated with other chromosomal aberrations most commonly t(4:14) and chromosome 13 deletion². The association of 1q21 gain and loss of chromosome 13 has been linked to the risk of conversion to overt disease⁵. In a case study of multiple myeloma patients it was discovered that 30% of chromosomal abnormalities mapped to chromosome 1, most up-regulated genes mapped to chromosome 1q and down-regulated genes to chromosome 1p⁶. Gains of the long arm 1q are one of the most common genetic abnormalities in multiple myeloma⁷ and duplications of the chromosome 1q band are frequently associated with disease progression^8,9.

In band 1p32.3 CDKN2C (P18) is a tumour suppressor gene responsible for inducing apoptotic cell death and DNA fragmentation¹⁰. It is up-regulated by the expression of the cytokine IL-6 in multiple myeloma and deletion of the gene is associated with a more proliferative disease. Although P18 deletions have been reported to be rare in human malignancy, cytogenetic analysis has shown abnormalities of 1p32-36 in 16% of human multiple myeloma¹⁰.

References:

1. Tasaka et al., Br J Haematology 1997;96(1):98-102
2. Fonseca et al., Leukemia 2006;20(11):2034-40
3. Cremer FD, Cancer Genet Cytogenet 2005;161(2):116-24
4. Hanamura I, Blood 2006;108(5):1724-32
5. Rosinol L, Br J Haematology 2005;130(5):726-32
6. Shaughnessy JD, Blood 2007;109(6):2276-84
7. Avet-Loiseau H, Genes Chromosomes Cancer 1997;19(2):124-33
8. Sawyer JR, Blood 1998;91(5):1732-41
9. Le Baccon P et al., Genes Chromosomes Cancer 2001;32(3):250-64
10. Kulkari et al., Leukemia 2006;16:127-34