Genomic characterization of the GATA3 mutational landscape in breast cancer.

• DOI: 10.1200/jco.2023.41.16_suppl.1039
• Publication Date: 2023-06-04T14:10:33Z
• Authors: Jason A Mouabbi; Funda Meric-Bernstam; Polina Turova; Konstantin Cherny...; Vladimir Kushnarev; Nikita Kotlov; Jessica H. Brown; Patrick Clayton; Krystle Nomie; Nathan Fowler; Debu Tripathy; Senthil Damodaran
• Keywords: GATA3

1039 Background: GATA3 expression is broadly used as a biomarker for diagnosing cancer of breast origin and its strongly associated with estrogen receptor (ER)-positive luminal phenotype. Although mutations are observed in 12-18% cancers (BC), they poorly characterized. Recently, the pharmacological inhibition MDM2 has been shown to significantly impair tumor growth GATA3-deficient models vitro, vivo, patient-derived xenograft harboring somatic mutations. Therefore, given potential targetability GATA3-mutated BC cells, it important better understand characterize mutational landscape help guide future prospective clinical studies. Methods: We accessed cohort samples profiled genomically transcriptomically from two open-source datasets: TCGA (n=961) METABRIC (n=1866). chi-squared test analyze frequency across PAM50 subtypes (Basal, HER2, Luminal A, B, Normal-like) histological (invasive ductal carcinoma [IDC] invasive lobular [ILC]). Mutations affecting other genes wild-type (WT) were compared using test. analyzed gene correlated different sites expression, amplification, co-occurring mutations, behavior. levels Mann-Whitney Results: Of 2,827 samples, unevenly distributed five subtypes, A B had highest (16% 17%, respectively) basal subtype no (p <0.0001). Further analysis showed that more common IDC than ILC (17% vs 8.7%; p While CBFB, AKT1, TBX3 ARID1A frequently TP53, CDH1 PIK3CA mutually exclusive (adjusted <0.0001 all genes). Analysis identified types GATA3: group truncating occurring at end (after 307 position including splice site 308) before position. The first was increased TP53 second little effect on behaved similarly WT. Conclusions: making them an ideal target trials involving inhibitors.