Browsing by Author "Casavilca-Sambrano, S"

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Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden
(Nature Publishing Group, 2018) Marchio, A; Cerapio, JP; Ruiz, E; Cano, L; Casavilca-Sambrano, S; Terris, B; Deharo, E; Dejean, A; Bertani, S; Pineau, P
In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1-6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas' indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.
GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms
(Springer Nature, 2022) Geng, X; Wang, C; Gao, X; Chowdhury, P; Weiss, J; Villegas, JA; Saed, B; Perera, T; Hu, Y; Reneau, J; Sverdlov, M; Wolfe, A; Brown, N; Harms, P; Bailey, NG; Inamdar K; Hristov, AC; Tejasvi, T; Montes, J; Barrionuevo, C; Taxa-rojas, L; Casavilca-Sambrano, S; de Pádua Covas Lage JLA; Culler HF; Pereira, J; Runge, JS; Qin, T; Tsoi, LC; Hong, HS; Zhang L; Lyssiotis, CA; Ohe, R; Toubai, T; Zevallos-Morales, A; Murga-Zamalloa, C; Wilcox, RA
Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America
(Nature Publishing Group, 2018) Cano, L; Cerapio, JP; Ruiz, E; Marchio, A; Turlin, B; Casavilca-Sambrano, S; Taxa-Rojas Luis; Marti, G; Deharo, E; Pineau, P; Bertani, S
We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.