Search

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.

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.

Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C --> G transition at 447 bp of p16exon3 and a T --> A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS.

The majority of gastric B-cell lymphomas histologically are classified as low grade mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas (DLBCL). There is evidence that the different histologic types are genetically heterogeneous, evolving through different pathogenetic pathways. Recurrent cytogenetic aberrations have been found in MALT lymphoma, whereas in DLBCL, limited cytogenetic data are available. We report here a DLBCL and a Burkitt-like gastric lymphoma case, cytogenetically studied by G-banding and M-FISH technique. In the first case, gains of chromosome 3, 7, 13, and 18 were found. An additional ring chromosome 1 identified as a clonal abnormality suggested clonal evolution. In the second case, trisomy 8, del(6)(q13), as well as t(8;14), t(1;5), and t(1;7), were observed. To our knowledge, cytogenetic data for gastric Burkitt-like lymphoma have not been reported, and M-FISH has not previously been used in the study of gastric lymphomas.

In six patients with breast cancer, uncultured tumor cells were investigated with G-banding and multicolor fluorescence in situ hybridization (M-FISH). A large number of numerical and structural aberrations could be analyzed. Among other structural abnormalities, reciprocal, hidden and complex translocations were found. Recurrent t(1;10) and t(6;16), not previously described, were identified, as well as t(15;22). The latter was also found in additional cases among our unpublished breast carcinomas. The significance of t(15;22) for breast cancer is discussed, taking into account also data drawn from the literature. Reciprocal translocations were a prominent feature in a pseudodiploid lobular carcinoma. Hidden translocations on 6p22∼p24 were detected with M-FISH. Involvement of 6p22∼p24 was observed in five cases. The analysis of various other translocations and different structural abnormalities revealed the following common breakpoints (according to frequency of involvement): 1p34∼p36, 3p12∼p13, 4p13→q11, 14p11→q11, 1q42, 8p11, 8q24, 10q22, 11q13, 11q23∼q24, 13q13, and 18p10∼p11. Loss of 3p and 1p34∼p36→pter and complete or partial loss of 13q and chromosome 17 were also found. With the combination of G-banding and M-FISH techniques, chromosome misclassification is avoided and the characterization of complex tumor karyotypes is more effective.

We describe a cervical teratoma revealed in the prenatal period that was studied cytogenetically. We were recently confronted with the case of a fetal solid neck mass suggestive of a teratoma. After termination of pregnancy the tumor was studied cytogenetically. This is the first case in the recent literature where a clone of cells with an additional chromosome marker has been detected. Cytogenetic study of the fetal blood in addition to cytogenetic study of the tumor after the termination of pregnancy showed the karyotypes 46,XY and 46,XY/47,XY + m, respectively. Fetal cervical teratoma is a rare condition. Genetic investigation in the case should be considered in order to reveal chromosome rearrangements.

We describe a patient with ulcerative colitis (UC) who developed small vessel vasculitis. Perinuclear antineutrophil cytoplasmic antibody myeloperoxidase (p-ANCA-MPO) positivity was detected along with a highly elevated titer of anticardiolipin antibodies. A total proctocolectomy was undertaken and the patient, more than 5 years later, remains in very good condition. The possible causative association between the UC, the p-ANCA-MPO-positive small vessel vasculitis, and the anticardiolipin antibodies is discussed.

The molecular events leading to the development of ovarian cancer are not well-established. Defects of the retinoblastoma protein (pRb)/cyclin-D1/p16 pathway have been shown to play a critical role in the development of human malignancies. In particular, the p16/cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosomal region 9p21 frequently is altered in several types of cancer.To investigate both the presence of numerical abnormalities of chromosome 9 and p16 gene alterations in ovarian cancer, we studied 28 cases by the fluorescence in situ hybridization (FISH) technique using a DNA p16 probe and an a-satellite probe specific for chromosome 9.Numerical abnormalities of chromosome 9 were found in all studied cases. Polysomy 9 was detected in 10 cases while monosomy 9 in seven cases. In 11 cases, there were two cell populations, one with polysomy 9 and the other with monosomy 9. In all cases, the p16 gene deletion was observed. Among them, 25 cases presented deletion of p16 gene in 21.43%-86.3% of the examined cells. Three cases carried deletion of the p16 gene in a lower proportion (12.04%-19.49%). In five cases with p16 gene deletion, homozygous deletion was detected.Numerical aberrations of chromosome 9 and p16 gene deletion are common findings in ovarian cancer. Data suggest that the p16 gene, located in the short arms of chromosome 9, may play a role in ovarian carcinogenesis. In addition, polysomy 9 could lead to activation of a number of oncogenes, thus participating in the neoplastic process in the ovaries.

The detection of recurring genetic changes in breast cancer can be extremely difficult. The tumors display very complex structural chromosomal rearrangements the origin of which are often very difficult to establish. The identification of recurrent chromosomal changes is a useful strategy for understanding tumorigenesis and specific chromosomal associations. Isochromosome i(5p) is a frequent finding in several types of cancer but it has been rarely described in breast cancer. The aim of the present study was to investigate the presence of i(5p) in primary breast tumors.Sixteen cases of breast cancer were cytogenetically studied by direct culture of cancerous cells and G-banding technique. We focused on structural aberrations of chromosome 5 in order to identify the presence of i(5p) in breast cancer.All the cases presented complex chromosomal changes with hyperploidization and various unidentified marker chromosomes being the prominent finding. Among 16 cases studied 6 cases presented an i(5p). No other structural abnormalities of chromosome 5 could be identified.The presence of i(5p) in breast tumors suggests that this chromosomal abnormality plays an important role in the development of breast cancer. Isochromosome 5p needs to be further molecularly analyzed as a candidate region for the isolation of genes related to carcinogenesis. Moreover, the fact that i(5p) has been described in several different tumor types suggests that there are no fundamental tissue-specific differences in the genetic mechanisms leading to tumorigenesis.

Lung cancer is one of the most common types of cancer worldwide and its pathogenesis is closely associated with various environmental exposures and gene alterations. The identification of genetic changes is a useful strategy toward understanding tumourigenesis and specific genetic associations. Since the tumor suppressor gene p16 located at 9p21 chromosomal region might have an important role in lung carcinogenesis, the aim of the present study was to investigate p16 gene alterations and numerical aberrations of chromosome 9 in non-small cell lung cancer.Nineteen cases of non-small cell lung cancer (11 squamous cell carcinomas, 6 adenocarcinomas and 2 large cell carcinomas) were investigated by fluorescence in situ hybridization (FISH) technique using a DNA p16 probe and alpha-satellite probe specific for chromosome 9.Polysomy 9 was found in 13 cases (6/11 squamous cell carcinomas, 5/6 adenocarcinomas and 2/2 large cell carcinomas). p16 gene alterations were found in 16 cases. Among them, deletion of p16 gene was found in 15 cases (8/11 squamous cell carcinomas, 5/6 adenocarcinomas and 2/2 large cell carcinomas). In six cases with p16 gene deletion, homozygous deletion was observed.Numerical aberrations of chromosome 9 and p16 gene deletion are common findings in all subtypes of non-small cell lung cancer. Despite suggesting the p16 gene in the 9p chromosomal region plays a role in lung carcinogenesis, the presence of other oncogenes reflected by polysomy 9 participating in the neoplastic process cannot be excluded. Data of the present study also suggest, that there might not be a fundamental relationship between genetic changes and histological subtype of non-small cell lung cancer.

Ovarian cancer represents the leading cause of death among patients with gynaecological cancer. The identification of chromosomal abnormalities is a useful strategy toward understanding tumourigenesis and specific chromosomal associations. Since single chromosomal changes might be primary events implicated in the initiation of the neoplastic process, the aim of the present study was to investigate the presence of simple structural chromosomal changes in ovarian cancer.Reviewing on ascetic effusions samples cytogenetically studied by direct culture of tumour cells and a G-banding technique, two ovarian cancer cases were found which presented simple structural chromosomal abnormalities.The first case presented an abnormal clone of cells with an acquired pericentric inversion of chromosome 9, inv(9)(p11q13), as a sole anomaly. The second case presented simple chromosomal changes with involvement of the Xq23 chromosomal region, while a translocation t(X;11)(q23;q23) was also defined.The significance of the acquired pericentric inversion 9 in the development of the neoplastic process remains unknown. The chromosomal regions Xq23 and 11q23 need to be further investigated in association with clinicopathological parameters in ovarian cancer. The documentation of more ovarian cancer cases with simple chromosomal abnormalities is considered of major importance facilitating the identification of candidate genes involved in the neoplastic process. Improving the molecular understanding of ovarian cancer development and progression could facilitate the detection of specific tumour subtypes.

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.

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.

In Philadelphia-negative chronic myeloproliferative disorders (CMPD), increased proliferation with effective maturation of the myeloid lineage is present, while peripheral leukocytosis, thrombocytosis or elevated red blood cell mass are found. This group of disorders includes polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Furthermore, cases that cannot be clearly defined are regarded as unclassified CMPD. In Philadelphia-negative CMPD, recurrent cytogenetic abnormalities occur, but no specific abnormality has been defined to date. Chromosomal abnormalities detected in a neoplastic disease as a sole anomaly are of major importance, possibly constituting primary changes implicated in the initiation or progression of the neoplastic process. The aim of this study was to investigate the frequency and the type of single chromosomal changes in Philadelphia-negative CMPD patients.By conventional cytogenetics, 245 Philadelphia-negative CMPD cases at diagnosis were investigated for the frequency and the type of single chromosomal aberrations.Seventeen patients presented single chromosomal changes. These aberrations were, according to frequency, +8 (in 3 PV cases, 2 IMF and 2 unclassified myeloproliferative diseases), +13 in 3 cases (IMF, ET and unclassified myeloproliferative disease), monosomy 10 in 2 PV cases, monosomy 14 in one ET patient, +3, -4 and del(11)(q13) in 1 unclassified myeloproliferative disease each and monosomy 7 in 1 IMF case.It is unclear whether these abnormalities found at the time of diagnosis play a role in CMPD. However, since an isolated chromosomal abnormality may be implicated in the initiation of the neoplastic process, the documentation of more cases of CMPD with single abnormalities at the time of diagnosis would facilitate the identification of candidate genes involved in the neoplastic process.

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.

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.

Essential thrombocythemia (ET) is a chronic myeloid disorder that is characterized by persistent thrombocytosis, thrombohemorrhagic symptoms and a low risk of transformation to leukemia. Chromosomal abnormalities in ET are very rare and most of the patients studied were either in leukemic transformation or they had received treatment with cytotoxic agents. The number of cases studied at the time of diagnosis is very limited. In the present study, 67 cases with ET, at the time of diagnosis, were cytogenetically studied by a G-banding technique. Among them, only four presented chromosomal abnormalities. In two cases, a del(5)(q13q33) was identified, accompanied by trisomy 20 in one case, while, in the other case, monosomy 17 and a small marker chromosome were additionally found. In each of the remaining two abnormal cases, clonal isolated trisomy 13 or monosomy 14 were found, respectively. Since these chromosomal abnormalities were found at the time of diagnosis, they might be related to the neoplastic process. The documentation of more cases of chromosomal abnormalities in ET at the time of diagnosis may facilitate the identification of candidate genes involved in the neoplastic process.

Chromosomal abnormalities characterize the biological behavior of acute myeloid leukemia (AML), also facilitating the identification of genes responsible for its development and/or progression. Isochromosome 5p, i(5p), represents a rare chromosomal abnormality described, to date, in only a few AML cases. In almost all the cases reported, the i(5p) was accompanied by other abnormalities. Here, a new case of AML, evolved from a myelodysplastic syndrome (MDS) with a clonal trisomy 8, is reported. The case presented the following karyotype: 46, XY[15]/47, XY, +8[4]/47,XY, +1(5) (p10)[3]/ 48,XY,+i(5)(p10)+8[3]. To our knowledge, this is the first reported case of AML to present a clone with an isolated i(5p). The cytogenetic findings supported the hypothesis that i(5p) may represent a primary abnormality, which characterizes a small subset of AML cases.

Bladder cancer is a heterogeneous group of tumors from both the biological and clinical points of view. Conventional cytogenetics and molecular genetic techniques have shown non-random aberrations in bladder cancer, while certain chromosomal changes have been found to be highly correlated with tumor grade or stage. The aim of this study was to evaluate, by fluorescence in situ hybridization (FISH), the numerical aberrations of chromosomes X and Y in bladder cancer, comparing the incidence of nuclei with aneusomies in different grades or histological stages of the tumors.The FISH technique, using DNA probes specific for chromosomes X and Y, was applied to 35 male bladder tumor specimens directly processed for cytogenetic study.Polysomies of chromosome X were observed in 25 out of the 35 cases examined (71.43%), while numerical aberrations of chromosome Y were observed in 22 out of the 35 cases (62.86%). Of those cases with numerical aberrations of chromosome Y, 13 had polysomy (37.14%), while in 9 cases, loss of Y was observed (25.71%). Statistical analysis showed that numerical aberrations on chromosomes X or Y were not linked to histological stage, while a probable correlation was observed between aneusomies X or Y and tumor grade. Comparing the results of PT1-grade III tumors with those of PT1-grade II, statistical analysis showed that aneusomies Y and, especially, polysomy Y were correlated with PT1-grade III tumors, p = 0.023 and p = 0.010, respectively. An uncertain correlation between polysomy X and PT1-grade III tumors was found, p = 0.070.Our results may suggest that the genetic instability associated with PT1-grade III tumors may account for the considerable potential for aggression of these tumors. However, to draw definite conclusions, a large number of cases must be studied.

Myelodysplastic syndrome (MDS) is a clonal disorder of the pluripotent hematopoietic stem cells which is characterized by ineffective and dysplastic hematopoiesis. The pathogenesis of MDS is not well defined and it appears that multiple genetic changes are involved. Several studies have shown that certain chromosomal abnormalities may be influenced by environmental factors, while differences in the incidence of certain aberrations in different areas have also been reported. The aim of this study was to investigate the frequency and the type of chromosomal changes in Greek primary MDS patients. Single chromosomal abnormalities were focused on as possibly being primary changes implicated in the initiation of the neoplastic process. Using conventional cytogenetics, 239 MDS patients were studied and 63 cases were found with an abnormal karyotype (26.36%). Among the cytogenetically abnormal cases, 46 patients presented single chromosomal abnormalities (73.1%). These aberrations were according to frequency +8 (28.57), del(5q), -7/del(7q) and +14 (6.35 each), i(17q) and del(11(q13) (4.76 each), +11, -Y, i(1q), del(8q), del(18p) and t(X;11) (1.59% each). In conclusion, the incidence of chromosomal abnormalities in Greek MDS patients was lower than that reported in the literature. The most common single anomaly was trisomy 8, while a relatively high incidence of an isolated +14 was also observed. Notably, this is the first time an isolated i(1q) has been described in the literature.

Objectives: Chronic lymphocytic leukemia (CLL) comprises a heterogenous group of at least two types of disease entities characterized by distinctive clinical, immunophenotypical and genetic features. The molecular mechanisms underlying the pathogenesis and the histological transformation of CLL are not well known. The INK4A/p16, a cyclin dependent kinase inhibitor has been considered as a tumor suppressor gene. Inactivation of this gene by homozygous deletions, mutations and hypermethylation occurs in a variety of human neoplasms. The aim of the present study was to determine the frequency of p16 gene deletions and mutations as well as the methylation status of the same gene in CLL patients. Methods: We examined 34 samples from CLL patients by Southern Blotting, Single-Strand Conformation Polymorphism (SSCP), DNA sequencing and Methylation-Specific PCR. Results: Southern Blot analysis revealed non-rearranged bands in 33/34 cases. Homozygous deletions were not observed in any case. In 1/34 case a rearranged band was detected with EcoRI enzyme. The PCR-SSCP analysis of exons 1 and 3 revealed normal pattern of migration in all cases examined. The analysis of exon 2 revealed abnormal migration pattern in 2/34 cases (5.8%). Sequencing of these cases revealed the presence of the ALA148THR polymorphism. Methylation analysis of p16 gene promoter revealed hypermethylation of CpG islands in 6/34 cases (17.6%). Conclusion: These results indicate that genetic alterations of p16 gene are rare events in patients with CLL. The clarification of the role of p16 gene promoter methylation in the pathogenesis and evolution of CLL needs further investigation.

Acquired clonal chromosomal abnormalities are found in about 30-50% of primary myelodysplastic syndromes (MDS). These abnormalities are predominantly characterized by total/partial chromosomal losses or gains and rarely by balanced structural aberrations. Trisomy 8 represents the most common chromosomal gain. In the present study, the numerical aberration of chromosome 8 was evaluated by the fluorescence in situ hybridization (FISH) technique in MDS, and the results compared with those of conventional cytogenetics. Thirty adult patients with primary MDS, 17 with a normal karyotype and 13 with several chromosomal abnormalities except chromosome 8, were included in this study. On comparing the results of FISH and conventional cytogenetics, a superiority of FISH over the karyotype was detected in 3 cases. In one of them, further cytogenetic analysis confirmed the FISH results. Nevertheless, the FISH technique has limitations, detecting only abnormalities specific for the target FISH probe used In clinical practice, conventional cytogenetics continues to be the basic technique for MDS patient evaluation. However, a large number of metaphases, even those of poor quality, must be analyzed in each case. The FISH technique could be considered to be complementary to achieve a more accurate analysis.

Ovarian cancer represents the leading cause of death among patients with gynecological cancer. The genetic changes underlying the initiation and progression of ovarian cancer have not been well defined. However, non-random structural chromosomal changes have been identified with common chromosomal breakpoints. We have studied cytogenetically 15 cases of ovarian adenocarcinomas by a direct culture of cancer cells and a G-banding technique investigating the presence of recurrent structural aberrations with common chromosomal breakpoints. Among very complex structural rearrangements found, we could recognize recurrent structural aberrations involving according to frequency chromosomal regions 3p13-14, 11p15, 19q13, 3q21, 11q23, 11q10, 1p13, 1p36, and 17q24-25. Isochromosomes i(5p), i(17q), i(8q) and i(11q) were also observed. Isochromosome i(5p), rarely reported in ovarian cancer was found in seven cases suggesting that it may be a novel recurrent abnormality. Translocations t(1;11), t(3;19), t(3;17), t(7;11) and t(11;17) were also identified. Conventional cytogenetics continues to be valuable detecting the presence of non-random chromosomal breakpoints and facilitating the identification of genes implicated in tumorigenesis.

Multiple myeloma (MM) is charecterized by great clinical heterogeneity. Among known prognostic factors the cytogenetic abnormalities are thought to be of major importance. The aim of this study was to correlate certain chromosomal abnormalities with immunoglobulin isotype and survival in MM patients.Forty-nine Greek MM patients, homogeneously treated with conventional-dose chemotherapy, were cytogenetically studied by direct culture of bone marrow cells and G-banding technique.Twenty-four patients had a normal karyotype while the remaining 25 patients presented numerical and structural abnormalities. Recurrent structural abnormalities were observed. Translocations involving the 14q32 region were observed in 8 cases, while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of chromosomal abnormalities on the overall survival of MM patients and we also showed that t(11;14) had a worse impact on disease outcome as compared to t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12) significantly worsened the prognosis in MM patients. No correlations existed between the association of immunoglobulin isotype with survival or certain chromosomal changes.Further studies are indicated at the molecular level to clarify the exact role and the prognostic value of 1p12 involvement in MM patients.

Bladder cancer is a genetically heterogeneous disease. The chromosomal aberrations observed are non-random and they are often correlated with disease progression. Several environmental risk factors have also been reported to be implicated in the pathogenesis of this disease. The aim of this study was to evaluate, by FISH technique, the numerical aberrations of chromosomes 9 and 11 in Greek bladder cancer patients and to correlate them with grade and histological stage of the tumors.FISH with a-satellite DNA probes specific for chromosomes 9 and 11 were applied to 35 primary bladder tumors directly processed for cytogenetic study.Numerical aberrations of chromosome 9 were observed in 23 out of 27 tumors (85.18%). Monosomy 9 was detected in 12 cases (44.45%) and polysomy in 11 cases (40.74%). Statistical analysis showed that polysomy 9 was linked to histological stage (p = 0.024) and grade (p = 0.01) of the tumors, while monosomy 9 was correlated with tumor stage (p = 0.050). Numerical aberrations of chromosome 11 were observed in 25 out of 35 cases (71.43%). Polysomy was detected in 24 cases (68.57%), while only one case (2.86%) had monosomy 11. Polysomy 11 was found mainly in high-grade and advanced-stage tumors.Numerical aberrations of chromosome 9 could be a potential biomarker for bladder cancer screening. Further studies must be carried out to investigate gene alterations reflected by numerical aberrations of chromosomes 9 and 11 also contributing to the classification of this disease.

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.

Gastric cancer is of major importance world-wide representing the second most common cause of cancer related death in the world. Data concerning the chromosomal changes in gastric cancer are limited and no specific change has been identified to date. We have studied cytogenetically 15 cases of primary gastric cancer by direct culture of tumors cells and G-banding technique. We focused on structural aberrations observed in order to identify non-random aberrations presenting common chromosomal breakpoints. Chromosomes most commonly involved were according to frequency 1,11,14,7,17,6,8 and 13. Chromosome 11 was involved as add(11)(p15), while the pericentromeric area of chromosome 14 was constantly participated in aberrations. Isochromosomes i(1q), i(8q), i(13q), i(14q) and i(17q) were constantly found. Furthermore translocations t(1;7), t(7;14), t(6;17) and t(5;14) were identified. Conventional cytogenetics continues to be valuable in cancer study detecting genomic areas potentially candidate for the isolation of genes related to carcinogenesis.

Background The aim of this study was to determine the value of small-bowel preparation for patients undergoing capsule endoscopy. Methods The study design was prospective, randomized, and controlled. Eighty patients referred for capsule endoscopy were randomized into two equal groups. Patients in Group A (mean age 54.40 [15.65] years) ingested 2 L of a polyethylene glycol/electrolyte solution 16 hours before the test, whereas patients in Group B (mean age 59.85 [14.58] years) prepared for the procedure by taking only clear liquids during the prior day. The primary outcome evaluated was the effect of bowel preparation on the quality of capsule images, as assessed with an objective scoring system in which cleansing was graded as ”adequate“ or ”inadequate“ by blinded examiners. A secondary outcome was the effect of bowel preparation on diagnostic yield. For this purpose, the results of capsule endoscopy were classified as positive findings, findings of uncertain significance, and no findings. Results Cleansing of the small intestine was considered ”adequate“ in 36 patients in Group A (90%) vs. 24 patients of Group B (60%) (p = 0.004). A diagnosis was established in 26 patients in Group A (65%) compared with 12 patients in Group B (30%) (p = 0.003). Conclusions Bowel preparation before capsule endoscopy improves visualization of the small intestine, which may lead to an improvement in diagnostic yield.

P27 encodes a member of Cip/Kip family of cyclin dependent kinase inhibitors, the inactivation of which has been implicated in the pathogenesis of various hematological neoplasias. We report on a novel point mutation of this gene identified in a case of unclassified myeloproliferative syndrome consisting of a T → C transversion at 821 bp of p27 exon 1, resulting in a Ile → Thr substitution at codon 119. The analysis of larger number of cases as well as the effect of this mutation on protein's function will help to clarify its significance in the pathogenesis of myeloproliferative syndromes.

During variceal bleeding, several factors may increase portal pressure, which in turn may precipitate further bleeding. This study investigates the early effects of endoscopic injection sclerotherapy (EIS) and endoscopic band ligation (EBL) on hepatic venous pressure gradient (HVPG) during acute bleeding and the possible influence in outcome. In 50 cirrhotic patients with bleeding esophageal varices treated with EIS (n = 25) or EBL (n = 25), we performed repeated HVPG measurements before and immediately after endoscopic treatment (time 0) and every 24 hours for a 5-day period. Endotherapy was continued until the varices were too small for further treatment. Both groups were comparable with regard to age, gender, Child-Turcotte-Pugh grade, and HVPG. In the EBL and EIS groups, a significant (P

Limited data are available on the genetic events underlying gastric cancer. Studying a few cases by conventional cytogenetic techniques, we previously reported that chromosome 8 might be frequently involved. The aim of our study was to evaluate the numerical aberrations of chromosome 8 in gastric cancer using fluorescence in situ hybridization (FISH).FISH, with an a-satellite DNA probe specific for chromosome 8, was applied to 37 primary gastric tumors directly processed for cytogenetic study.Numerical aberrations of chromosome 8 were observed in 23 out of 37 tumors (62.16%). Trisomy was detected in 16 cases (43.24%), tetrasomy in 4 cases (10.81%) and monosomy in 3 cases (8.10%). No correlation was found between polysomy 8 and the histopathologic characteristics of the tumors.An increase in the number of chromosome 8 may frequently occur in gastric cancer. Advanced and more aggressive gastric tumors did not harbor polysomy 8. Further studies at molecular and clinical level must be carried out to identify the gene alterations reflected by polysomy 8 and possibly to facilitate the detection of specific tumors subtypes.

Certain constitutional translocations have been described to be associated with an increased risk of malignant diseases. We report here two patients, one with acute myeloid leukemia (AML) and another with biphenotypic acute leukemia, in whom constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) were observed, respectively. To our knowledge, none of the above translocations has been previously reported.

Chromosomal abnormalities are of significance in the study of hematologic malignancies. We describe one case of myelodysplastic syndrome (MDS) diagnosed 22 years ago as polycythemia vera (PV) as well as a case of unclassified myeloproliferative disease (MPD) with a poor clinical course. Both patients presented del(11)(q13) as the sole clonal abnormality. This abnormality was also found in two additional cases of MDS. Summarizing the literature, only ten other cases of myeloid malignancies with deletion of 11q involving band q13 as the sole anomaly have been reported. All but one of these cases presented interstitial deletions.

The Mixed Lineage Leukemia (MLL) gene has been identified in 11q23 translocations. The aim of the present study is the investigation of the frequency of MLL gene rearrangements in cases of de novo myelodysplastic syndromes (MDS). Sixty-two patients with de novo MDS were included in the analysis. The detection of MLL gene rearrangements was performed by Southern blot. Clonal karyotypic abnormalities were found in 15/50 (30%) cases. 11q23 abnormalities were not detected. One case with RAEB and a complex karyotype presented a del (11)(q13); further analysis by FISH revealed loss of one copy of MLL gene in all metaphases. Southern blot revealed germline bands in all cases using Eco RI and in 61/62 cases with Bam HI. The case with RAEB and a del (11)(q13) revealed a rearranged band following only Bam HI digestion, but not Eco RI. Rearrangements of MLL gene within exons 5-9 were not identified in this series of adult de novo MDS, indicating that this molecular abnormality is not involved in the pathogenesis of this group of hemopoietic disorders.

Cytogenetic studies of bladder cancer have shown several nonrandom aberrations. Numerical aberrations of both sex chromosomes were investigated in 32 primary bladder tumors with bicolor fluorescence in situ hybridization (FISH). Loss of chromosome Y and overrepresentation of chromosome X were observed in subgroups of male patients. Chromosome X was represented normally in female patients. Two of the above primary bladder tumors, a transitional cell carcinoma (TCC) and an adenocarcinoma, were further analyzed with both multiplex FISH (24-color M-FISH) and G-banding. Both cases exhibited 1) common breakpoints on 5q11 approximately q12 and 15q24; 2) involvement of the pericentromeric area of chromosome 13; 3) structural abnormalities of chromosomes 8 and 17, with loss of material on the short arm; 4) structural abnormalities involving chromosome 11; and 5) loss of chromosome Y. The TCC case also exhibited structural abnormalities of chromosome 9, resulting in loss of 9q. The combined G-banding and M-FISH findings could help reveal regions potentially involved in bladder tumorigenesis.

The different genetic alterations observed in diffuse and intestinal types of gastric cancer suggest that these two pathological types may represent different disease entities. We present two cases of primary gastric carcinoma, a well-differentiated intestinal type adenocarcinoma and a poorly differentiated diffuse type adenocarcinoma, both studied by a 24-color multiplex fluorescence in situ hybridization technique (M-FISH). The well-differentiated intestinal type adenocarinoma exhibited fewer structural abnormalities with five noncomplex translocations, deletions of chromosomes 5q, 6q, and 17q and an i(8q). In the case of poorly differentiated diffuse carcinoma, structural abnormalities predominated and normal homologues were mostly absent. But there were also similarities between the two cases: translocations on 1p and 9p; structural abnormalities of chromosome 8 with consistent loss of 8p; structural abnormalities of 12q; partial loss of chromosome 17 and 18; and polysomy of chromosome 20. This study shows that M-FISH is valuable in identifying hidden structural abnormalities and could, therefore, be useful in the investigation of primary solid tumors.

In a case with splenomegaly of unknown origin and features of hypersplenism, an interstitial 9q deletion was identified as a sole clonal abnormality of bone marrow cells. The meaning of 9q deletion as a primary change, as well as its clinical significance, are considered.

We present here 3 of 30 cases of large bowel cancer cytogenetically studied, with deletion of chromosome 5. One of them presented a terminal deletion and the other two an interstitial deletion of chromosome 5q. In all three cases the segment 5q12-22 was deleted. Our findings may show that the segment 5q12-22 is important for a subgroup of colorectal cancers.

A case of acute nonlymphocytic leukemia (M4) secondary to treatment for multiple myeloma is described. The patient presented a translocation t(1;3)(p36;q21) and monosomy 7.

We describe the cytogenetic findings in 11 gastric cancer cases. Nine cases showed a variable number of numerical and structural aberrations, while two cases had a normal karyotype. The chromosomes most frequently involved are chromosome 3 in six cases, 6 in four cases, and 13 in three cases. They mainly exhibited structural aberrations. An additional segment on chromosome 3p was observed in three cases, while two cases had a del(3q). A der(5) chromosome resulting from a translocation between chromosomes 3 and 5 was observed in two cases. Both cases had also a del(6q), a der(12), and an add(17p) chromosome as common abnormalities. Deletion of 6q chromosome distal to band 6q21 was observed in three cases. Trisomy 8 as a sole anomaly was found in one case. Our cytogenetic findings are discussed in relation to the reported in the literature data.

We report here one of 15 cases of acute lymphoblastic leukemia (ALL) cytogenetically studied, with hypodiploidy, a variant Ph translocation, and der (9) and der (19) chromosomes. The patient, a 14-year-old girl, underwent combination chemotherapy and bone marrow transplantation and is still in remission 22 months after transplantation.

We report 2 of 80 cases of myelodysplastic syndromes (MDS) cytogenetically studied, with involvement of chromosome 13. The first case had a t(6;13), and the second had a t(1;13). Abnormalities of chromosome 13 mainly involving loss of band 13q14 have been described in hematologic malignancies. In both our cases band 13q14 did not participate in the deleted segment.

Thirty cases of breast cancer were cytogenetically studied by G-banding using direct tumor preparations. Among them 20 cases exhibited abnormalities of the long and/or short arm of chromosome 11. Thus, 11q was involved in 16 cases and 11p in ten cases. There was consistent involvement of bands 11q23–24 (15 cases) and 11p15 (9 cases), where the cellular oncogenes ets and H- ras 1, respectively, are located. These findings suggest that involvement of bands 11q23–24 and 11p15 may be specific in a group of breast cancers, leading to the activation of cellular oncogenes or loss of cancer suppressor genes.

Cytogenetic findings of a primary renal-cell carcinoma are reported. The chromosome number was near triploid and there was tetrasomy for the long arm of chromosomes #1 and #3. The following structural chromosomal abnormalities were identified by the G-banding technique: i(1q), t(3;17), 6q−, 7p+, and a ring chromosome of unknown origin. Chromosomes #1, #3, #6, #7, and #17 involved in this case are often implicated in malignancy.