Analysis of Allelic Loss of Tumor Suppressor Gene ING4 in Plasma Cell Dyscrasias.
Connie Qi, Jiang Nancy, Lei Yu, Ning Yi, Hong Chang. University Health Network, Toronto, Canada; University of Maryland, Baltimore
Background: ING4 (Inhibitor of growth 4) is a member of the ING family of tumor suppressor proteins. ING4 gene, localized to chromosome 12p13.31, is frequently deleted and down regulated in variety of human solid tumors. However, it is largely unknown for its status in plasma cell disorders.
Design: Clonal plasma cells were evaluated for ING4 deletion status by fluorescence in situ hybridization (FISH) in patients with newly diagnosed multiple myeloma (MM), monoclonal gammopathy with undetermined significance (MGUS) (a pre-MM stage), and plasma cell leukemia (PCL). Common myeloma associated genetic aberrations including chromosome 13q deletion, 17p(p53) deletion, and t(4;14) were also evaluated in these patients.
Results: Interphase-FISH analysis detected hemizygous ING4 deletions in 7 of 89 (8%) MM patients and 4 of 17 (24%) PCLs, but none of the 15 MGUS patients had this deletion. ING4 deletions were detected in 5 of 7 (71%) MM patients at diagnosis with stage III disease (Durie-Salmon). Of 11 cases with ING4 deletions, 6 (55%) had coexistence of p53 deletions, including 3 of 7 (42%) MM, and 3 of 4 (75%) PCL cases. In contrast, 11% of MM and 50% of PCL harbored p53 deletions without ING4 deletions. There was no association between ING4 deletion and 13q deletion or t(4;14) translocation in MM or PCL.
Conclusions: Our results indicate that allelic loss of ING4 is uncommon in MM but appears more frequent in PCL. ING4 deletions tend to occur in advanced disease, be associated with p53 deletion, and absent in MGUS, suggesting that they are secondary, rather than primary events associated with disease progression in MM.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 247, Tuesday Morning