Detection of copy number aberrations in endometrial cancer using array CGH

Endometrial cancer, is the most common gynecologic malignancy in the developed countries. Prognosis varies based on the histologic subtype and other clinical pathologic features (stage, tumor grade, LVSI). However, the determination of histological subtype and grade is unreliable, particularly in high-grade tumors, misclassified cases have already been reported. Early diagnosis of the cancer is essential for the treatment and prognosis.

We identified three imbalanced regions using aCGH, 3p22.1 (41281477-41281777), 4q31.3 (153269677-153269977) and 5q22.2 (112164360-112164659). In combination of BAC clones to target these three regions, it is possible to develop a FISH panel to identify endometrial cancer. For further research endometrial cells will be collected through vaginal smears and analyzed by FISH panel to confirm the imbalances.

33.8 % of our endometrial cancer samples harbored LOH. The most common regions are 4p15.2p15.1, 10q22.2q22.3, 10q25.2q26.11, 11q22.3q23.2, 12q24.13q24.22 and 17q12q21.2, suggesting that tumor suppressor genes located within these regions might be involved in the pathogenesis of endometrial cancer. 

Two imbalanced areas were identified to distinguish between two histological types, 16q22.1 (67937732-68100313) and 13q13.1 (32950650-32950950). Approximately half of the cases could be correctly classified. 

We identified CNVs in endometrial related oncogenes and tumor suppressor genes. Particularly, the rule of CNVs tumorigenesis in CTNNB1, ARID1A and POLE genes are consistence with other previous studies. We established a classification scheme in combination of histological type, array-based CNVs and microsatellite status to recapitulate the TCGA molecular classification of endometrial cancer. Compared with the TCGA classification, the distribution of CNVs in serous like group and MSS group are highly consistent.

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