Abstract 460: Understanding transcriptomic profiles that might explain discordance of the PAM50 and immunohistochemistry classification methods in luminal tumors from Colombian women

Autor: Silvia J. Serrano-Gomez, Jone Garay, Oscar Garcia, Jovanny Zabaleta, María Carolina Sanabria-Salas, Laura Fejerman, Juan Carlos Mejía
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:460-460
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2019-460
Popis: Background: Breast cancer is the most common cancer in Colombian women. Five intrinsic subtypes have been described based on gene expression profiles and genetic signatures, such as PAM50, have been developed to classified tumors with different prognosis. In Colombia, we have previously reported that the most prevalent breast cancer subtype was luminal B based on immunohistochemistry (IHC) surrogates, which are routinely used in the clinical practice. We analyzed the concordance between IHC surrogates and PAM50 classification in luminal tumors from Colombian women and explored gene expression differences that may account for the observed differences. Methods: We performed whole-transcriptome RNA-seq analysis in 46 breast cancer samples from Colombian women diagnosed with estrogen receptor positive tumors (27 luminal A and 21 luminal B) at the Colombian National Cancer Institute. Genefu package from R was used to perform PAM50 classification, and the DESeq2package was used to test differential gene expression between discordant cases between PAM50 and IHC. Genes with adjusted p value less than 0.05 were considered statistical significant. Results: We found that 23 patients (50%) were discordant between both methodologies (IHC and PAM50). For the 27 luminal A tumors assessed by IHC, 10 (37%) were re-classified as luminal B by PAM50 and 3 (11.11%) as normal-like. On the other hand, for the 21 tumors classified as luminal B by IHC, 4 (19.04%) were re-assigned as HER2-enriched, 4 (19.04%) as luminal A and 2 (9.5%) as normal-like. Next, we tested differential expression in discordant vs. concordant cases with PAM50 within each luminal subtype assessed by IHC. For luminal B IHC-tumors, we found 67 differentially expressed genes. Some of the top differentially expressed genes are part of the ERBB2 signaling pathway (ERBB2, padj < 0.01, log2FC = 2.5; GRB7, padj < 0.01, log2FC = 2.95), which is consistent with the re-assignment of luminal A tumors to luminal B. Moreover, we found overexpression of ARID5B (padj< 0.01, log2FC=1.72) a histone modifier gene that has been described mutated in breast cancer. This result might suggest that an epigenetic mechanism may be involved in defining the luminal profile of these tumors. On the other hand, for luminal A IHC-tumors, we found 12 differentially expressed genes. The gene with the highest fold-change was DSCAM-AS1 (padj = 0.030, log2FC=3.43) which is very interesting as it is a estrogen-regulated long noncoding RNA (lncRNA) that has been recently associated with tumor progression and tamoxifen resistance. Conclusions: Our results suggest that epigenetic mechanisms such as histone modifications and the lncRNAs might be associated with luminal tumors in Colombian women and might also define the fate of the luminal profile of these tumors. Citation Format: Silvia J. Serrano-Gomez, Maria Carolina Sanabria-Salas, Jone Garay, Juan C. Mejia, Oscar Garcia, Jovanny Zabaleta, Laura Fejerman. Understanding transcriptomic profiles that might explain discordance of the PAM50 and immunohistochemistry classification methods in luminal tumors from Colombian women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 460.
Databáze: OpenAIRE
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