Alterações no número de cópias genômicas em carcinomas de mama

• Ano de defesa: 2013
• Autor(a) principal: Tavares, Ana Carolina Tomaz [UNESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Genoma humano; Expressão gênica; Câncer - Prognóstico; Human genome
• Link de acesso: http://hdl.handle.net/11449/108627

Breast cancer (BC) is a heterogeneous both at molecular and clinical level. Patients with similar clinical and histopathological findings can present different prognosis. Analysis of large scale genomic changes have helped to identify regions and genes associated with the various stages of mammary tumorigenesis. The present study aimed to evaluate the genomic profile by Comparative Genomic Hybridization array-based (aCGH), using the platform 4x180K (Agilent Technologies) in 53 primary invasive ductal carcinomas (IDC). The IDC showed 3849 genomic alterations, with similar proportion of genomic gains and losses (1,622 and 1,731, respectively), 444 alterations were found with high copy number gains (12%) and 52 homozygous losses (1%). We were identified 19 significantly recurrent genomic alterations in more than 20% of tumors. Losses were detected at 1p36.32, 8p23.3, 8p23.1, 8p11.23, 11q25, 14q11.1-q11.2, 16q23.3, 16q24.1 and 18q23, and gains at 1q21.1, 1q21.2, 1q22, 1q32.1, 1q42.3, 1q44, 8q24.21 and 15q11.2. The most frequent alterations were gains at 8q24.21 (36%) and 1q44 (32%), and losses at 8p11.23 (28.3%). Gains in 1q21.1-1q21.2 were associated with negative estrogen receptor (ER-) (P = 0.016) tumors. Loss on 8p23.1 was associated with longer disease-free survival (P = 0.027). Losses on 8p23.3 were associated with HER2 + tumors (P = 0.033) and high level of Ki67 (P = 0.036). Gain at 8q24.21 was associated with lower risk of lymph node involvement (P = 0.0199). Loss at 14q11.1-q11.2 was associated with more aggressive tumor characteristics such as grade III (P = 0.0147), high level of Ki67 (P = 0.0096) and worse clinical outcome, with metastasis development (P = 0.0375). Loss at 18q23 was associated with progesterone receptor negative (PR-) (P = 0.0065) tumors. The comparison of the genomic alterations according to receptor status ER, PR and HER2, lymph node involvement (LN) and development of distant metastases (DM) revealed ...