Estabelecimento e caracterização citogenética de linhagem celular de carcinoma adenoide cístico

Abstract

Adenoid cystic carcinoma (ACC) is a rare neoplasm that mainly affects the head and neck regions, especially salivary glands. Growth is slow, but with but with a propensity to perineural invasion, local postoperative recurrence and metastasis. The most used treatment for this type of tumor is surgery followed by postoperative radiotherapy. The molecular characteristics of ACC are unclear, and unfortunately, the rarity of this type tumor limits to obtain in vitro and in vivo models that contribute in the investigation of pathogenesis and more efficient treatments. In the present study, a cell line was established and characterized for the evaluation of anticancer molecules. For this, it was obtained tissue samples of ACC off the tubular histological subtype from the retromolar trigone and a blood sample from a 59-year-old female patient. Array Comparative Genomic Hybridization (aCGH) performed molecular cytogenetic characterization in tumor tissue and cell line, while blood was genotyped for ancestry. Cell culture established from the collected tumor tissue showed rapid growth of tumor colonies from passage 18, stabilizing at passage 30. Blood genotyping revealed an ancestral contribution of 19% Amerindians, 31.5% Europeans and 49.5% of blacks. In cytogenetic analysis, gains were observed in loci harboring important genes such as EGFR (7p22.1-p11.2), BRAF (7q32.3-q34), HER2 (17q12-q21.2) and SMARCA1 (xq25-q27.1). Also in the lineage, loss (6q23.3-q25.1, PLAGL1 gene locus) and deletion (9p21.3-p21.1, CDKN2A/B gene locus) were observed; In tissue, only gains were observed (9q34.3, NOTCH1 locus and 5q32, PDGFRβ locus). The loss in 19p13.3-p12, locus of the CDKN2D gene, stands out as a common event in both samples. These findings corroborate other studies in the literature and make the established lineage a good in vitro model that can assist in the investigation of the pathogenesis of CAC and the basic research for new therapeutic modalities.