Identificação de marcadores moleculares de resposta à quimioterapia neoadjuvante e associação de radioterapia e quimioterapia em pacientes com carcinoma epidermóide de orofaringe
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Data
2010-08-26
Autores
Rosa, Luciana Albina Reis [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Os relatos em literatura que relacionam preditores biológicos de resposta à radioterapia e ou quimioterapia em carcinomas de orofaringe (CEO) são limitados e a maioria se baseia em grupos de tumores de diferentes sítios anatômicos. Os objetivos deste estudo foram investigar marcadores biológicos que poderiam atuar como potenciais preditores de resposta à quimioterapia de indução seguido de radioterapia, e associá-los com o padrão de infecção pelo HPV e dados clínico-patológicos. Trinta e sete casos de CEO foram avaliados quanto à infecção pelo HPV, 32 casos para alterações no número de cópias (CNAs) por CGH-array e 22 casos tiveram seu perfil de expressão gênica avaliado em relação ao tecido normal e adjacente da orofaringe. O subtipo HPV16 foi o mais prevalente entre eles (8/37), seguido do HPV18 (2/37) e HPV26 (2/37) e HPV16/18 (1/37). As análises de CGH-array foram realizadas na plataforma 4x180k (Agilent). A análise dos dados foi realizada usando o programa Nexus Copy Number v5.0 (Biodiscovery) e seguido de comparação com o Database of Genomic Variants. Foram identificadas 3222 alterações no número de cópias genômicas (CNAs) com prevalência de perdas heterozigotas (46,6%), seguida de ganhos (40,7%), alto nível de ganhos (7,9%) e perdas homozigotas (4,8%). As alterações mais frequentes envolveram ganhos em 3q, 5p, 8q, 9q e 11q e perdas em 3p, 5q, 8p, 9p e 18q. Os casos HPV negativos (20) apresentaram um maior número de CNAs (média 117 CNAs/caso) comparadas aos pacientes HPV positivos (12), os quais apresentaram um perfil genômico menos complexo (média 73 CNAs/caso). Foram identificadas regiões genômicas capazes de diferenciar os tumores HPV positivos e negativos (P<0,05), entre elas as perdas em 7q22.1 e 14q12 presentes exclusivamente nos tumores HPV...
There are few reports relating biological predictors of response to radiotherapy and or chemotherapy in oropharyngeal squamous cell carcinomas (OSCC), and most of them are based on different head and neck anatomical sites. The aims of this study were to investigate biological markers that could act as potential predictors of response to chemotherapy of induction followed by radiotherapy, and its association with HPV infection and clinicopathological data. Thirty-seven OSCC were evaluated for HPV genotyping, 32 cases for copy number alterations (CNAs) by array CGH and 22 cases were investigated by large scale transcription analysis. The subtype HPV16 was the most prevalent among them (8/37), followed by HPV18 (2/37) and HPV26 (2/37), and HPV16/18 (1/37). The array CGH analysis were performed using the 4x180k platform (Agilent). Data analysis were done by Nexus Copy Number v5.0 (Biodiscovery) software and compared with Database of Genomic Variants. A total of 3222 copy number alterations (CNAs) were identified with a prevalence of heterozygous loss (46.6%), followed by gains (40.7%), high level of gains (7.9%) and homozygous loss (4.8%). The most frequent gains involved 3q, 5p, 8q, 9q and 11q and losses on 3p, 5q, 8p, 9p and 18q. The HPV-negative cases (20) showed a higher number of CNAs (average 117 CNAs/case) compared to HPV-positive cases (12), which showed a less complex genomic profile (in average 73 CNAs/case). Genomic regions were able to differentiate between HPV positive and negative cases (P<0.05), including losses on 7q22.1 and 14q12, which were detected exclusively in HPVpositive tumors (P=0.044). A comparative analysis between the cases treated with carboplatin associated with RT (22 cases) was done aiming to identify chromosomal regions that could... (Complete abstract click electronic access below)
There are few reports relating biological predictors of response to radiotherapy and or chemotherapy in oropharyngeal squamous cell carcinomas (OSCC), and most of them are based on different head and neck anatomical sites. The aims of this study were to investigate biological markers that could act as potential predictors of response to chemotherapy of induction followed by radiotherapy, and its association with HPV infection and clinicopathological data. Thirty-seven OSCC were evaluated for HPV genotyping, 32 cases for copy number alterations (CNAs) by array CGH and 22 cases were investigated by large scale transcription analysis. The subtype HPV16 was the most prevalent among them (8/37), followed by HPV18 (2/37) and HPV26 (2/37), and HPV16/18 (1/37). The array CGH analysis were performed using the 4x180k platform (Agilent). Data analysis were done by Nexus Copy Number v5.0 (Biodiscovery) software and compared with Database of Genomic Variants. A total of 3222 copy number alterations (CNAs) were identified with a prevalence of heterozygous loss (46.6%), followed by gains (40.7%), high level of gains (7.9%) and homozygous loss (4.8%). The most frequent gains involved 3q, 5p, 8q, 9q and 11q and losses on 3p, 5q, 8p, 9p and 18q. The HPV-negative cases (20) showed a higher number of CNAs (average 117 CNAs/case) compared to HPV-positive cases (12), which showed a less complex genomic profile (in average 73 CNAs/case). Genomic regions were able to differentiate between HPV positive and negative cases (P<0.05), including losses on 7q22.1 and 14q12, which were detected exclusively in HPVpositive tumors (P=0.044). A comparative analysis between the cases treated with carboplatin associated with RT (22 cases) was done aiming to identify chromosomal regions that could... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Boca - Cancer, Virus do papiloma, Carcinoma de celulas escamosas, Biologia molecular
Como citar
ROSA, Luciana Albina Reis. Identificação de marcadores moleculares de resposta à quimioterapia neoadjuvante e associação de radioterapia e quimioterapia em pacientes com carcinoma epidermóide de orofaringe. 2011. 176 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências de Botucatu, 2011.