1.
Bardi, G, et al.
(författare)
Tumor karyotype predicts clinical outcome in colorectal cancer patients
2004
Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 22:13, s. 2623-2634
Tidskriftsartikel (refereegranskat) abstract
Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.
2.
Diep, Chieu B, et al.
(författare)
Genome characteristics of primary carcinomas, local recurrences, carcinomatoses, and liver metastases from colorectal cancer patients
2004
Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 3
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in the Western world, and despite the fact that metastases are usually the ultimate cause of deaths, the knowledge of the genetics of advanced stages of this disease is limited. In order to identify potential genetic abnormalities underlying the development of local and distant metastases in CRC patients, we have, by comparative genomic hybridization, compared the DNA copy number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal carcinomatoses, and 42 liver metastases from 61 CRC patients. RESULTS: The median number of aberrations among the primary carcinomas, local recurrences, carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease. With hierarchical cluster analysis, liver metastases could be divided into two main subgroups according to clusters of chromosome changes. CONCLUSIONS: Each stage of CRC progression is characterized by a particular genetic profile, and both carcinomatoses and liver metastases are more genetically complex than local recurrences and primary carcinomas. This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.
3.
Johansson, Bertil, et al.
(författare)
Clinical and biological importance of cytogenetic abnormalities in childhood and adult acute lymphoblastic leukemia
2004
Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 36:7, s. 492-503
Forskningsöversikt (refereegranskat) abstract
Among the approximately 7,000 cytogenetically abnormal childhood and adult B- and T-lineage acute lymphoblastic leukemias (ALL) published to date, numerous recurring chromosomal aberrations and abnormality patterns have been identified, and it has been clearly shown that the cytogenetic features often correlate closely with specific morphologic, immunophenotypic, and clinical parameters. Thus, karyotypic investigations are now routinely performed for diagnostic and prognostic purposes in ALL, with the chromosomal abnormalities/cytogenetic patterns playing a major role for proper risk assessment and choice of treatment. At the same time, the cytogenetic analyses have resulted in the identification of more than 70 different genes, located at the breakpoints of ALL-associated structural chromosomal abnormalities, that are causally implicated in the leukemogenic process. Hence, the genetic studies have also improved our understanding of the mechanisms of leukemogenesis. However, the almost staggering amount of cytogenetic information presently available has made it increasingly difficult to obtain a general overview of the clinical and biological importance of karyotypic patterns in ALL. Here, we summarize and review the cytogenetic features of childhood and adult ALL, with emphasis on their molecular genetic consequences and their clinical impact.
