ABSTRACT
Osteosarcoma (OS) is a primary malignant tumor of bone. Despite the successful use of multiple chemotherapeutic agents in the treatment of OS, more than 30% of OS tumors remain resistant to treatment. Elucidation of cellular resistance mechanisms may lead to better treatments for cancer patients. In this study, we used the low-density expression cDNA array, GEArray Q Series Human Cancer Drug Resistance and Metabolism Gene Array to screen genes related to drug resistance in 15 OS tumors. Expression patterns of the MPV gene were validated by real time PCR on 45 OS patient tumor samples and correlated with clinical and pathological data. Major vault protein (MVP) expression was present in 24 (53%) tumor samples and absent in 21 (47%). Samples from surgery showed correlation between the expression of MVP, metastatic disease at diagnosis and event free survival (EFS). The MVP gene expression correlates with metastatic disease at diagnosis after neoadjuvant chemotherapy (p=0.048), and is also associated with worse EFS (p=0.036). These findings suggest that MVP expression is involved in one of the mechanisms of drug resistance in OS and is induced by chemotherapy.
Subject(s)
Bone Neoplasms/genetics , Gene Expression , Osteosarcoma/genetics , Vault Ribonucleoprotein Particles/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Child , Child, Preschool , Disease-Free Survival , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Profiling , Humans , Infant , Male , Neoadjuvant Therapy , Oligonucleotide Array Sequence Analysis/methods , Osteosarcoma/metabolism , Osteosarcoma/secondary , RNA, Messenger/metabolism , RNA, Neoplasm/analysis , Reverse Transcriptase Polymerase Chain Reaction , Vault Ribonucleoprotein Particles/metabolismABSTRACT
OBJECT: The purpose of this study was to examine chromosomal gains and losses in 11 pediatric adamantinomatous craniopharyngiomas by using comparative genomic hybridization (CGH), as well as to review the cytogenetic literature that has contributed to the characterization of these tumors. One source of confusion in the cytogenetic and CGH literature concerning craniopharyngioma is that the authors of most studies fail to distinguish between pediatric and later-onset forms of the disease. Thus, this study was focused on pediatric craniopharyngioma. METHODS: To determine an overview of the genetic events leading to the development of these tumors, 10 adamantinomatous craniopharyngiomas were analyzed using CGH; none of the tumor specimens demonstrated gains or losses of DNA sequence. CONCLUSIONS: In view of these findings as well as those published in the majority of previous cytogenetic studies of craniopharyngiomas, the authors conclude that the recurrent acquisition of chromosomal imbalances does not play a major role in tumorigenesis and that chromosomal gains and losses are a relatively rare event in primary tumors of pediatric origin.
Subject(s)
Chromosome Aberrations , Craniopharyngioma/genetics , DNA, Neoplasm/analysis , Pituitary Neoplasms/genetics , Adolescent , Age of Onset , Cell Transformation, Neoplastic/genetics , Child , Child, Preschool , Chromosomal Instability , Cytogenetics , Female , Humans , Male , Nucleic Acid Hybridization , RecurrenceABSTRACT
Os autores relatam um caso de aconselhamento genético para uma família na qual uma translocaçäo equilibrada foi identificada no pai de uma criança malformada que faleceu sem ter sido estudada citogeneticamente. Uma gestaçäo posterior foi reconhecida cocmo normal após realizaçäo de diagnóstico pré-natal e dela nasceu uma menina normal
Subject(s)
Infant, Newborn , Humans , Male , Female , Translocation, Genetic/genetics , Genetic Counseling , Karyotyping , Pedigree , AmniocentesisABSTRACT
Neste trabalho, apresentamos intervalos de referência para a concentraçäo de alfafetoprotéina (AFP) em líquido amniótico (LA) de gestantes brasileiras de alto risco. O conhecimento destes valores em várias idades gestacionais é um pré-requisito para o diagnóstico dos defeitos de fechamento do tubo neural, dentre outras malformaçöes fetais graves. As alteraçöes de tubo neural representam os primeiros exemplos de defeitos multifatoriais passíveis de serem diagnosticados "intra utero", graças à dosagem de AFP. Este é um trabalho pioneiro no Brasil e acreditamos que a AFP possa ser dosada nas condiçöes existentes nos laboratórios brasileiros, através do sistema de imunoeletroforese em "rocket". Esta determinaçäo possibilita o diagnóstico precoce de certas anomalias fetais graves, cuja importância, em nosso meio, näo deve ser desprezada