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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 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.

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.

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.

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.

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.

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

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.

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.

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.

A case of malignant lymphoma with a partial duplication of the long arm of chromosome #1, as well as 14q+ and 11q+ marker chromosomes, is presented. The coincidence of this duplicated segment of chromosome #1 with others described in the literature supports the idea that this specific chromosome segment may be related to the malignant process.

Ten cases of primary rectosigmoidal adenocarcinoma were cytogenetically studied by G-banding technique using direct tumor cell preparations. All cases exhibited both numerical and structural chromosomal aberrations. Chromosomes commonly involved were, according to frequency, #3 and #8 (eight cases each), #1 (seven cases), #6 (six cases), and #7 (five cases). Similar or identical marker chromosomes were frequently identified, and it is noteworthy that i(8q) was found in five out of ten cases studied. The possible specificity of chromosome 8q in rectosigmoidal adenocarcinomas is discussed.

Cytogenetic analysis of a biopsy specimen taken during sigmoidoscopy from an adenocarcinoma of the large bowel revealed a hypodiploid karyotype with numerical and structural abnormalities identified as trisomy 7, t(3;12), t(1;17), interstitial deletion of the long arm of a chromosome #5 and loss of the Y chromosome with double X chromosomes. The possibility of this karyotype being a further evolutionary step in a subgroup of large bowel cancers and the clinical value of the above findings are discussed.

Cytogenetic analysis was performed in five cases of intestinal type gastric carcinoma. Three cases were near-diploid and two others were near-triploid. The chromosomes involved were: #9 (four cases), #8 (three cases), #1, and #7 (two cases each). The nonrandom chromosomal abnormalities included aberrations of chromosome #9 as trisomy or i(9q) or 9p+ marker chromosome and excess of 8q material (i.e., trisomy or i(8q) chromosome). Our results indicate that abnormalities of chromosome #9 are a common feature in a subgroup of intestinal type gastric cancers and that there are common cytogenetic abnormalities in gastric and large bowel cancer.

Ten patients with multiple myeloma (MM) were studied cytogenetically, using the G-banding technique. It was found that five patients had a normal karyotype, whereas five patients exhibited various chromosomal abnormalities. The presence of marker chromosomes was a consistent finding. Among those, the 14q+ marker chromosome was present in three cases, partial or complete trisomy for 1q was detected in four cases, and chromosome #6 was involved in two cases. In one case the 14q+ marker chromosome was determined to result from a translocation between chromosomes #11 and #14. In one patient with Bence Jones kappa multiple myeloma, there was a translocation between chromosomes #2 and #8.

A combined haematological, ultrastructural and chromosomal study was made in 20 patients with preleukaemia. There was evidence of specific correlations between (a) Hb F levels and pancytopenia or profound anaemia, (b) chromosomal and electron microscopic findings and (c) thrombocytosis and ringed sideroblasts. The above findings might be of importance in identifying subgroups of preleukaemic patients with different prognosis.