Abstract 2267: Alterations in TGFβ signaling in ovarian cancer patients with TGFβ receptor 1 variants

Transforming growth factor β (TGFβ) signals through the TGFβ Receptor 1 (TGFβR1) and is implicated in many aspects of malignancy. TGFβR1 gene is frequently mutated in ovarian carcinomas (OvCa) (Chen, T., et al, Cancer Research 61, 4679-4682, 2001). Susceptibility to numerous cancers is linked to two germline variants of TGFβR1, a G to A single nucleotide polymorphism in intron 7 (Int 7G24A) and a nine base pair deletion in exon 1 (TGFβR1*6A) although the mechanism(s) for this association is still unclear. Since the canonical pathway for TGFβR1 signaling is via phosphorylation of SMAD, the goal was to determine the association of either or both variants with development of subtypes of OvCa and to measure phosphorylation of pSMAD in the epithelium and stroma of OvCas from women with either or both Int 7G24A and TGFβR1*6A. FFPE tissues from 122 women without a history of cancer, and 59 women with OvCa were obtained from St. Elizabeth Healthcare (N. KY) and from 63 women with OvCa through the Cooperative Human Tissue Network (Birmingham Ala). OvCa patients and non-cancer controls were age matched. St. Elizabeth Healthcare IRB gave permission for this study. Tumors were diagnosed in HE 57.7% of OvCa patients had a TGFβR1 variant vs. 36.6% of controls. Frequency of TGFβR1 variants in 62 patients with Type 2 OvCa was 62.9%. Patient survival differed significantly between patients with LMP, Type 1, and Type 2 OvCa (p Citation Format: Julia H. Carter, James P. Schaeper, Taiping Chen, Diane W. Fritz, Leah Focke, Adrian Guy, James A. Deddens, Larry E. Douglass. Alterations in TGFβ signaling in ovarian cancer patients with TGFβ receptor 1 variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2267.