ABSTRACT
In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene. Another region spanning 22q11-q13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome. Coordinate 22q11-q13 alterations were observed in 9 of 11 tumors with the 9q34 alteration. Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-q31.3 were found associated with this instability only in tumors from patients with a smoking history. Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations. Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.
Subject(s)
Colorectal Neoplasms/genetics , Gene Dosage , Genes, abl , Genomic Instability , Proto-Oncogene Proteins c-bcr/genetics , Adult , Aged , Aged, 80 and over , Chromosomes, Artificial, Bacterial/genetics , Chromosomes, Human, Pair 14/genetics , Chromosomes, Human, Pair 22/genetics , Chromosomes, Human, Pair 7/genetics , Chromosomes, Human, Pair 9/genetics , Female , Humans , Male , Middle Aged , Nucleic Acid Hybridization , Oligonucleotide Array Sequence AnalysisABSTRACT
El propósito del presente estudio fase I y II en el Instituto Roswell Park Memorial fué el mejorar las respuestas clínicas en pacientes con adenocarcinoma Matastático de Cólon y Recto utilizando la combinación de 5FU (600 mg./M2) y dosis altas de dL-CF (500 mg/M2) con la adición de Cisplatino. Debido a las dosis bajas de Cisplatino que se utilizan, se puede anticipar que las náuseas y vómitos severos no se presentan, por lo tanto la dósis de Cisplatino se administra en forma directa en lugar de administrar la por infusión contínua