A novel p27 gene mutation in a case of unclassified myeloproliferative disorder.

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 821bp 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.

Absence of MLL gene rearrangement in de novo myelodysplastic syndromes (MDS).

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 study of 11 gastric adenocarcinomas.

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.

Acute lymphoblastic leukemia with a variant Philadelphia translocation, der(9), and der(19) chromosomes.

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.

Interstitial 9q deletion. A primary change in a case with splenomegaly of unknown origin.

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.

Involvement of chromosome 13 in myelodysplastic syndromes.

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.

Myelopathies during the course of multiple myeloma.

BACKGROUND: The development of acute non-lymphoblastic leukaemia (ANLL) or myelodysplastic syndromes (MDS) secondary to treatment of multiple myeloma (MM) is well known. In some cases the simultaneous appearance of MM and ANLL has been described. METHODS: In this series the simultaneous appearance of MM and various myelopathies in 91 untreated patients with MM, and the development of myelopathies during the course of the disease in 72 treated patients were studied. RESULTS: Simultaneous appearance of MM (IgA/lambda) and refractory anaemia with ring sideroblasts (RAS) was observed in one case (1.1%). Development of myelopathies in treated patients with MM was found in 4 out of 72 cases (cumulative risk at 8 years 28.3%). In one case (IgG/lambda MM) a myeloproliferative disorder (MPD) developed 6 years after the initial diagnosis. Cytogenetic analysis was normal. In the second patient (IgG/k MM) a similar MPD was observed 5 years after the initial diagnosis. The karyotype was 46, XX, -5 + t (20;?). The third patient with lambda light chain disease developed RAS 11 months after the initial diagnosis. The karyotype was 46, XY/hypodiploidy + M. Finally, the fourth case (IgG/k MM) developed ANLL (M4) 28 months after the initial diagnosis and the karyotype was 45, XX, -7, t(1;3). CONCLUSIONS: The simultaneous appearance of MM and various myelopathies is unusual and probably represents a neoplastic transformation of a single progenitor in both lymphoid and myeloid malignancies. On the contrary, the development of myelopathies during the course of treated patients is a common phenomenon. The time of development and the cytogenetic findings strongly suggest that they are related to treatment with cytostatics.

Involvement of chromosome 5 in large bowel cancer.

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.

Preferential involvement of 11q23-24 and 11p15 in breast cancer.

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.

Translocation (1;3)(p36;q21) in secondary leukemia.

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.

Atypical location of extramedullary hematopoietic masses in thalassemia.

A case of beta-thalassemia with multiple foci of extramedullary hematopoiesis (EH) is reported. EH masses were demonstrated in the presacral and the costovertebral space. EH foci were also encountered in the spleen.

Cytogenetic study of rectosigmoidal adenocarcinomas.

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.

Common cytogenetic findings in primary breast cancer.

Five cases of breast cancer were cytogenetically studied by G-banding, using direct tumor preparations. Chromosomes involved in aberrations, according to frequency, were #1, #11, #3, #6, #5, and #17. In all five cases there were abnormalities of chromosomes #1 and #11. In each case chromosome #1 was involved in at least two different ways. In four cases abnormalities of chromosomes #11 exhibited nonrandom involvement of band q22-23. These findings confirm the role of chromosomes #1 and #11 in breast cancer and show that band 11q22-23, which has been reported to be an inheritable fragile site and is a specific breakpoint in acute leukemia, also may be specific in a group of breast cancer. Thus, correlation of an inheritable fragile site and a malignant disease with familial incidence seems possible.

Common cytogenetic findings in gastric cancer.

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.