Methods and kits used in classifying adrenocortical carcinoma
a technology for adrenocortical carcinoma and a kit is applied in the field of methods and kits used in the classification of adrenocortical carcinoma, which can solve the problems of severe side effects, only showing a response in approximately 22% of patients, and mitotane, the only drug compound approved for acc treatment,
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example 1
Identification of Genes Expressed in the G2 / M Phase as Potential Biomarkers of Outcome in ACC
[0073]Previous gene expression studies have focused on identifying gene expression signatures that differentiate ACC from benign adrenal adenomas and normal adrenal tissue (See References 5, 6, 8, 9, 15, and 16). IGF2, FGFR1, FGFR2, FGFR4, and TOP2A have been shown to have a greater degree of expression in ACC while CDKN1C, KCNQ1, ADH1, IGFBP6, IGFR1, and ABCB1 show decreased expression in ACC (See References 9, 15, and 18). A panel of genes related to IGF2 signaling and steroidogenesis is almost as good as the Weiss score at predicting recurrence (See Reference 5) and two additional studies have shown that ACC can be subdivided into two groups with differences in survival based on gene expression profiles. (See References 6 and 8). A two-gene signature, PINK1 and BUB1B has been shown to be associated with poor prognosis (See Reference 6).
[0074]Expression profiling was performed on 20 ACC tu...
example 2
PTTG1 is a Biomarker of Decreased Survival in ACC
[0089]PTTG1 encodes the protein securin. Securin is involved in the G2 / M transition of the cell cycle by inhibiting the activity of separase through phosophorylation. It is degraded by the anaphase-promoting complex, releasing the inhibition of separase and promoting sister chromatid separation. Securin has also been implicated in the negative regulation of p53 through phosphorylation of p53.
[0090]PTTG1 was identified as a target of interest through expression profiling of 20 ACC tumor samples. PTTG1 was identified as differentially over-expressed 3-5 fold on both the Affymetrix U133 Plus 2 and the Agilent Human 1A Oligo Microarray (v2) platforms. Analysis of that data identified the G2 / M transition, particularly sister chromatid separation, as being dysregulated. One such gene that showed coordinate expression with CDC2 was PTTG1. PTTG1 was the sole gene tested to show a significant association between the level of expression and sur...
example 3
PTTG1 Expression Correlates with a Cluster of ACC Tumors Likely to have Poor Survival
[0092]Examination of data from Giordano T J et al, Clin Cancer Res 15, 668-676 (2009) showed that expression of PTTG1 did not significantly correlate with survival and therefore teaches away from this invention (FIG. 3). Giordano does report the presence of ACC tumor clusters. FIG. 4 shows that tumors classified as Cluster 1 have a poor survival outcome. Tumors classified as Cluster 2 have a better survival outcome. While PTTG1 expression does not directly correlate with survival, PTTG1 does directly correlate with cluster expression. FIG. 5 shows that tumor cluster 1 has higher PTTG1 expression than tumor cluster 2.
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