Evaluation of the NKD-1 mutation in carcinoma of the uterine endometrium.

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e15537 Background: Misregulation of the WNT/β-catenin pathway is characteristic of some cancers, most notably colorectal and endometrial cancer. For example, mutations in the CTNNB1 gene occur in at least 15% of endometrial cancers. However, stabilization of the β-catenin protein occurs more frequently in endometrial cancers (∼40% of cases) suggesting that mutations in other WNT pathway components may lead to misregulation of this pathway in endometrial cancer. Naked cuticle (NKD) proteins inhibit WNT signaling, and hence, alteration of NKD gene activity in mammals might activate WNT. A recent study showed that NKD1 exon 10 mutations were frequent in colorectal cancers (primary tumors and cell lines) that did not harbor mutations in other WNT/β-catenin pathway components, raising the question as to whether mutations in NKD1 gene might also be significant in endometrial carcinogenesis. We thus sought to evaluate whether NKD1 mutations also characterize endometrial adenocarcinoma. Methods: Genomic DNA was extracted from 3 endometrial cancer cell lines and 53 primary endometrial tumor samples from patients at UT Southwestern hospitals. Exon 10 of the NKD1 gene was subjected to bidirectional PCR sequencing. Automated base calls generated by sequence analysis software were visually inspected to confirm accurate variant detection. Results: Of the 53 endometrial tumor samples evaluated, 29 were endometrioid, 10 carcinosarcoma, 3 clear cell, 4 mixed, and 7 were of unclassified histology. No NKD1 mutations including single base insertions or deletions of the exon-10 poly-(C)7 tract were identified that would result in the synthesis of truncated NKD1 protein, as has been shown to occur in colorectal adenocarcinomas. Conclusions: No NKD1 gene mutations were found in any uterine cancers, arguing that other defects in this pathway account for the frequent stabilization of β-catenin. No significant financial relationships to disclose.