13,14 Taurine is an essential constituent of bile and plays a vital role in the function phase 3 of a variety of tissues.15 Studies in mice and rats have shown abundant CDO1 in adipose tissue, liver, brain, and kidney.16�C18 Accumulation of cysteine because of low CDO1 activity is associated with cytotoxicity and neurotoxicity.19�C22 Altered CDO1 levels have been observed in several cancers. Booken et al23 found that CDO1 is upregulated in Sezary syndrome, a highly malignant form of cutaneous T-cell lymphoma. In contrast, most studies reported decreased CDO1 expression in cancer. Hypermethylation within the CDO1 promoter with concomitant decreased expression has been observed in colon and breast cancer, and is also a predictor of poor prognosis in breast cancer.

24,25 Promoter hypermethylation and expression of CDO1 has not been investigated to date in sarcomas. Recently, an epigenetic reactivation screen carried out in our laboratory using cell lines derived from PLSs identified CDO1 as a potential target of epigenetic regulation. In the current study, analysis of pre-existing microarray data confirmed variable expression of the CDO1 gene in patients with complex karyotype liposarcomas. The findings were validated in a larger cohort of liposarcomas by quantitative RT-PCR and immunohistochemistry (IHC). The CDO1 expression level was analyzed relative to the histological subtype, location, and whether the tumor was primary or recurrent. Finally, promoter methylation and CDO1 expression were studied in a cohort of liposarcoma specimens and during differentiation of human mesenchymal stem cells (hMSCs) into mature adipocytes.

Our results suggest that CDO1 is a marker of liposarcoma progression and adipogenic differentiation. Methods Patients and tissue samples A total of 64 de-identified complex karyotype liposarcoma specimens were obtained from the MD Anderson Cancer Institute, Fox Chase Cancer Center, and the Cooperative Human Tissue Network (CHTN) under Institutional Review Board-approved protocols for banking of excess tissue from patients undergoing surgical resections or biopsy following informed consent. In all, 32 cases were WDLS, 20 cases were DDLS, and 12 cases were PLS. All tissue specimens were kept frozen at ?80��C before RNA extraction or paraffin embedding. The pathology report for each case was examined for age, sex, tumor location (retroperitoneum, extremity), and presentation (primary, recurrent). A WDLS/DDLS tissue microarray (TMA) was built consisting of a total of 572 paired WDLS/DDLS cores from 394 surgeries on 256 patients. Of the cores on the TMA, 157 are DDLS and 415 are WDLS. This TMA was constructed as previously described for PLS and myxoid/round cell liposarcoma arrays (PMID 21598240; Brefeldin_A PMID 22020193).