Preferential involvement of chromosome 11 as add(11)(p15) in ovarian cancer: Is it a common cytogenetic abnormality in cancer?

Ovarian cancer represents the leading cause of death among patients with gynecological cancer. The genetic changes underlying the development and progression of ovarian cancer are not well defined. Identification of chromosomal aberrations is a useful strategy toward understanding tumorigenesis and specific chromosomal associations. Studying 15 ovarian cancer cases by conventional cytogenetic techniques, we previously reported that 11 p 15 was the most consistent chromosomal breakpoint involved. The aim of the present study was to investigate the presence of structural changes of chromosome 11 in ovarian cancer. Ten cases of ovarian cancer were cytogenetically studied by direct culture of tumour cells and G-banding technique. Eight cases presented structural aberrations of chromosome 11 with 11 p 15 involved as add(11)(p 15) in all 8 cases and 11q23 involved as add(11)(q23) in 3 cases. Findings of the present study further support the possible role of chromosomal abnormalities add(11)(p 15) and add(11)(q23) in ovarian cancer. These aberrations may result either in loss of genetic material from 11p and 11q, respectively, or in specific genes alterations. It is necessary, these chromosomal regions to be further investigated at molecular and clinical level. Improving the molecular understanding of ovarian cancer development and progression could facilitate the detection of specific tumor subtypes and contribute also to novel strategies for the management of ovarian cancer patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved

Cytogenetic and molecular aspects of Philadelphia negative chronic myeloproliferative disorders: Clinical implications

Chronic myeloproliferative disorders (CMPD) are clonal disorders of the hematopoietic stem cell. The myeloid lineage shows increased proliferation with effective maturation, while peripheral leukocytosis, thrombocytosis or elevated red blood cell mass are found. In Philadelphia negative CMPD recurrent cytogenetic abnormalities occur, but no specific abnormality has been defined to date. The spectrum of cytogenetic aberrations is heterogeneous ranging from numerical gains and losses to structural changes including unbalanced translocations. The most common chromosomal abnormalities are 20q-, 13q-, 12p-, +8, +9, partial duplication of 1q, balanced translocations involving 8p11 and gains in 9p. Cytogenetic analysis of CMPD by conventional or molecular techniques has an important role in establishing the diagnosis of a malignant disease, adding also more information for disease outcome. Molecular studies may detect the possible role of candidate genes implicated in the neoplastic process, addressing new molecular target therapies. FIP1L1/PDGFR alpha rearrangements, as well as alterations of PDGFR beta or FGFR1 gene have been found to be associated with specific types of CMPD. Recently, a novel somatic mutation, JAK2V617F, has been reported in most of the polycthemia vera (PV) patients, as well as in a lower percentage in essential thrombocythemia (ET) or idiopathic myelofibrosis (IMF) patients. This finding represents the most important advance in understanding of the molecular mechanisms underlined the pathogenesis of CMPD, contributing to the classification and management of patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved

Cytogenetic and molecular aspects of gastric cancer: Clinical implications

Gastric cancer is of major importance world-wide being the second most common cause of cancer-related death in the world. According to Lauren’s histological classification gastric cancer is divided in two groups, the better differentiated intestinal carcinomas and the poorly differentiated diffuse-type cancers. The genetic changes underlying the initiation and progression of gastric cancer Lire not well defined. Gastric carcinogenesis is a multistep process involving a number of genetic and epigenetic factors. Although it has been proposed that different genetic pathways exist for differentiated and undifferentiated carcinomas, the two histological subtypes of gastric cancer share some common genetic alterations. Currently, tumor histology and pathologic stage are the major prognostic variables used in the clinical practice for gastric cancer patients. However, it is known that tumors with similar morphology may differ in biological aggressiveness, prognosis and response to treatment. Molecular genetic analysis of gastric cancer revealed a number of associations of certain genetic changes with pathological features, tumor biological behavior and prognosis of gastric cancer patients, suggesting that these genetic abnormalities might play an important role in gastric tumorigenesis. Increasing evidence suggests that the molecular genetic changes could be helpful in the clinical setting, contributing to prognosis and management of patients. Regarding epigenetic events in gastric tumorigenesis, a number of methylating markers have been proposed for risk assessment, prognostic evaluation and as therapeutic targets. However, further research is required in order to systematically investigate the genetic changes in gastric cancer estimating also their usefulness in the clinical practice. A good understanding of the genetic changes underlying gastric carcinogenesis may provide new perspectives for prognosis and screening of high risk individuals. Some of the genetic alterations could definitely improve tumor classification and management of gastric cancer patients. Also, based on molecular data identified in gastric cancer novel therapeutics might help to improve the treatment of this disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Janus kinase 2 mutations in Philadelphia negative chronic myeloproliferative disorders: Clinical implications

The chronic myeloproliferative disorders (CMPD) are a group of clinically related diseases characterized by clonal hematopoiesis with increased proliferation of one or more myeloid cell lineages. The identification of JAK2 mutations (JAK2V617F and JAK2 exon 12) in patients with CMPD is of great significance in the understanding of the molecular mechanisms underlined the pathogenesis of the disease contributing also to clinical management of patients. However, the precise pathogenetic contribution of JAK2 mutation is far from being fully elucidated and it is currently under intense investigation. Testing of JAK2 mutations has made the diagnosis of CMPD more precise than ever before, while genotype-phenotype associations have been identified. Furthermore, the discovery of JAK2 mutations facilitated the development of new targeted therapies and clinical trials are currently ongoing. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented

Cytogenetic and molecular aspects of lung cancer

Lung cancer is one of the most common cancers worldwide and its pathogenesis is closely associated with tobacco smoking. Continuous exposure of smoking carcinogens results in the accumulation of several alterations of tumorigenesis related genes leading to neoplastic bronchial lesions. Lung cancer is divided in two main histological groups, non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep process in which a number of genetic events including alterations of oncogenes and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung cancer are very complex. However, a number of recurrent cytogenetic abnormalities have been identified. Many of these changes are common in both major histological groups of lung cancer while certain chromosomal abnormalities have been correlated with the stage or the grade of the tumors. In addition, several molecular alterations have been constantly found. Some of them are common in different histological subtypes of lung cancer and they appear to play an important role in the pathogenesis of lung cancer. A good understanding of the underlying genetic changes of lung tumorigenesis will provide new perspectives for early diagnosis and screening of high-risk individuals. In addition, a number of genetical prognostic factors have been identified as possibly helpful parameters in the evaluation of lung cancer patients. Further research is required in order to systematically investigate genetical alterations in lung cancer contributing to improvement of lung cancer classification and staging and to development of new molecular targeted therapies. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Cytogenetic aspects of adult primary myelodysplastic syndromes: Clinical implications

Myelodysplastic syndrome (MDS) is a heterogeneous disease from the clinical, biological and morphological point of view. The pathogenesis of MDS is not well established and it appears to occur complex changes in the stem cell biology. Clonal chromosomal aberrations are found in 30-50% of primary MDS and no specific cytogenetic abnormality has as yet been defined. The chromosomal abnormalities are predominantly characterized by partial/total chromosomal losses or chromosomal gains. These chromosomal abnormalities include mainly -5/del(5q), -7/del(7q), del(11q), del(12p), del(20q), -Y, and +8. The role of cytogenetic analysis in the diagnosis, prognosis, taking treatment decisions and follow up of patients with MDS has been clearly defined. Despite its difficulties in obtaining for analysis high quality metaphases conventional cytogenetics continues to be the basic technique for cytogenetic evaluation of a MDS patient. Other molecular cytogenetic methods have been shown to be complementary, without replacing the information obtained with this technique. Further investigations with both conventional and molecular cytogenetics in relation to clinical features as well as other molecular methods will undoubtedly contribute to improve understanding of the underlying genetic events responsible for the development and evolution of MDS leading to more accurate classification and management of MDS patients. (c) 2005 Published by Elsevier Ireland Ltd