10 - Correlating Copy Number Alterations in Dedifferentiated Liposarcoma With Tumor Behavior and Patient Outcome

Abstract

Dedifferentiated liposarcoma (DDLS), as a most common intermediate- to high-grade lipomatous neoplasm, has metastatic potential and much poorer prognosis than atypical lipomatous neoplasm/well-differentiated liposarcoma (ALN/WDLS). Although tumor location and grade of DDLS have been shown to have prognostic significance, knowledge of genetic alterations for prognosis of DDLS remains limited. Genetic abnormalities underlying the pathogenesis and behavior of DDLS are not well understood. The aim of this study is to evaluate the correlation of specific CNAs with DDLS behavior and patient outcome to identify prognostic markers for risk stratification of liposarcoma patients. FFPE tumor tissues from 47 DDLS with clinical and pathological information were obtained for DNA extraction and cytogenomic microarray analysis (CMA) using a cancer-specific genomic microarray designed by Cancer Genome Consortium (CGC). The results show that copy number alterations including chromosomal gains, amplifications, and losses were very common in DDLS. Amplification of genes (defined as 5 or more copies) within the 12q13-15 region were most common as previously described. CNAs in 12 regions of interest were compared with DDLS FNCLCC grade and clinical disease status. Unlike the findings in previous studies by FISH, Q-PCR, and MLPA in DDLS, our study using CMA showed that higher levels of amplification of MDM2 correlate with an increased risk of adverse event including local recurrence, metastasis, and/or death related to disease in our cohort of DDLS patients. In addition, higher levels of MDM2 amplification were also significantly more likely to be found in retroperitoneal tumors compared to all other sites. Similar to findings in previous studies, we also found that high amplification levels of CDK4 correlated with increased risk of any adverse event related to disease and decreased disease specific survival. Correlations of other copy number alterations with DDLS tumor behavior and prognosis will also be reported and discussed.