Cancer Genetics and Cytogenetics最新文献

To quantify the expression of HMGA1 mRNA in uterine leiomyomas, the expression of HMGA1 was analyzed in a series including tumors with aberrations of chromosome 6 (n = 7) and cytogenetically normal tumors (n = 8) as a control group by quantitative reverse transcriptase–polymerase chain reaction. The average expression level in the 6p21 group was found to be 5.6 times higher than that in the control group, and with one exception, all cases with 6p21 alteration revealed a high expression of HMGA1 mRNA than cytogenetically normal tumors. Nevertheless, compared to fibroids with a normal karyotype, the upregulation of the HMGA1 mRNA in these cases was much less strong than that of HMGA2 mRNA in case of 12q14∼15 aberrations identified in previous studies.

We characterized the cytogenetic changes and prognostic characteristics of 133 Korean patients with myelodysplastic syndrome (MDS), focusing on 5q− syndrome and MDS with chromosome abnormalities involving 5q deletion according to World Health Organization 2008 classification. In all patients, G banding and fluorescence in situ hybridization for 5q were performed, and in MDS patients with 5q deletion, the deleted region on chromosome 5 was mapped with fluorescence in situ hybridization for EGR1, CSF1R, and PDGFRB. The frequency of isolated del(5q) syndrome and 5q deletion was 2.2% (3 of 137 patients) and 15.3% (21 of 137 patients), respectively. International Prognostic Scoring System (IPSS) groups were low risk (5.8%), intermediate 1 (51.1%), intermediate 2 (27.8%), and high risk (15.3%). The patients with del(5q) were significantly older (62 years) and showed an unfavorable survival compared to patients without del(5q). Half (53%) of the patients with del(5q) also had complex chromosome abnormalities, including chromosome 7 abnormalities. Of the patients with del(5q), 93.3% were deleted for all three regions on 5q, compared to 66.7% of patients with isolated del(5q). Marker chromosomes proved to be chromosome 5 with interstitial deletion of q arm by fluorescence in situ hybridization in three patients. The biological characteristics of MDS in Korea seem to be markedly different from those of Caucasians, with Koreans having a younger age, lower frequencies of 5q− syndrome, higher frequencies of complex cytogenetic abnormalities including del(5q), and poorer prognosis. We infer that additional chromosome abnormalities contribute to the adverse prognostic impact in patients with del(5q).

Patients diagnosed with t(8;21)-acute myeloid leukemia (AML) are currently considered to have good prognoses, but about half of these patients relapse. FLT3-internal tandem duplication (ITD) is generally thought to be strongly associated with poor prognosis in AML, but is rarely reported in patients with t(8;21)-AML. Expression of the neural cell-adhesion molecule (CD56) is also associated with a significantly shorter complete remission duration and survival in patients with t(8;21)-AML. Patients with t(8;21)-AML expressing CD56 have been reported to exhibit a higher incidence of granulocytic sarcoma (GS), and t(8;21)-AML with GS results in a less favorable prognosis than AML with this translocation alone. Here, we report on a 15-year-old girl with t(8;21)-AML having both CD56 expression and FLT3-ITD. This patient underwent unrelated donor bone marrow transplantation and achieved complete remission, but thereafter presented with obstructive jaundice caused by GS compression of the common bile duct without bone marrow invasion at relapse. Autopsy revealed multiple nodules of the stomach membrane and invasion into the head of the pancreas. For earlier detection of relapse, we suggest that it would be useful to examine existence of GS in CD56-positive t(8;21)-AML patients at diagnosis and hematologic remission. Even though t(8;21)-AML is less likely to co-occur with FLT3-ITD in pediatric patients, this report suggests that prognostic factors, including FLT3 and KIT genes and the surface marker CD56, should be analyzed in these patients.

Upper urinary tract tumor (UUTT) usually presents a high grade and stage, and recurs frequently. The aim of this study was to evaluate the utility of a fluorescence in situ hybridization (FISH) assay on chromosomes 3, 7, 9, and 17 as a reliable and noninvasive method for the diagnosis of Chinese patients with UUTT. Urine specimens from 50 patients with UUTT and 25 donors without evidence of urothelial tumors were analyzed by cytology and FISH. Voided urine samples from 20 normal individuals were used to establish the cut-off values for FISH assay. The McNemar test was applied for sensitivity and specificity. The overall sensitivity of FISH was statistically significantly greater than that of cytology (84.0 vs. 40.0%, P=0.000). The overall specificities of FISH and urine cytology were all 96.0% (P=1.000). Polysomy in chromosomes 3, 7, and 17 were 38, 42, and 30%, respectively. Heterozygous and homozygous loss of the p16 locus was found in 36 and 32%, respectively. FISH analysis performed on cells collected from voided urine is feasible, and FISH could prove to be a reliable and less invasive ancillary test and improve the sensitivity of urine cytology in the diagnosis of UUTT.

The survival rate for children with osteosarcoma (OS) has improved dramatically with the introduction of multiagent chemotherapy. As the number of pediatric cancer survivors increases, there is a concern about the development of secondary malignant neoplasms. Secondary acute myeloid leukemia (AML) has been rarely reported after treatment for OS. We describe a 14-year-old boy with OS of the left ileum who developed secondary AML 15 months after completion of treatment. Cytogenetic analysis of the leukemic cells demonstrated deletion 11q23, whereas fluorescence in situ hybridization revealed rearrangement of the MLL gene. Only the addition of the long-distance inverse polymerase chain reaction technique identified the SEPT2 as the MLL fusion partner resulting in t(2;11)(q37;q23) that was reported in a very few secondary AML cases. Because of the cryptic nature of MLL translocations that cannot be detected by conventional cytogenetics or may misinterpreted as deletion, additional molecular techniques are required to identify the precise translocation partner. Because long-distance inverse polymerase chain reaction is not available in most molecular laboratories, the true incidence of t(2;11)(q37;q23) and the involvement of SEPT2 as the MLL translocation partner could be more prevalent in secondary AML.

Metakaryotic cells and syncytia with large, hollow, bell-shaped nuclei demonstrate symmetrical and asymmetrical amitotic nuclear fissions in microanatomical positions and numbers expected of stem cell lineages in tissues of all three primordial germ layers and their derived tumors. Using fluorescence in situ hybridization, mononuclear metakaryotic interphase cells have been found with only 23 centromeric and 23 telomeric staining regions. Syncytial bell-shaped nuclei found approximately during weeks 5–12 of human gestation display 23 centromeric and either 23 or 46 telomeric staining regions. These images suggest that (1) homologous chromatids pair at centromeres and telomeres, (2) all paired telomeres join end-to-end with other paired telomeres in all mononuclear and some syncytial metakaryotic cells, and (3) telomere junctions may open and close during the syncytial phase of development. Twenty-three telomeric joining figures could be accounted by 23 rings of one chromatid pair each, a single pangenomic ring of 23 joined chromatid pairs, or any of many possible sets of oligo-chromatid pair rings. As telomeric end-joining may affect peri-telomeric gene expression, a programmed sequence of telomeric end-joining associations in metakaryotic stem cells could guide developmental arboration and errors in, or interruptions of, this program could contribute to carcinogenesis.

Among patients with acute myeloid leukemia (AML), the t(6;9) (p22;q34) is a rare but defined subset with a poor prognosis. We report 16 patients with the t(6;9), of whom 13 had AML, 2 had myelodysplastic syndrome (MDS), and 1 had chronic myeloid leukemia in myeloid blast crisis (CML-BC). All except for one were evaluated at diagnosis. The median age was 34.5 (range: 7–62 years), with 12 adults and 12 males. Trilineage dysplasia was present in 13 (81%). Marrow basophilia was seen in only two patients, one of whom had CML-BC. HLA-DR was positive in all 12 patients assessed, CD33 in 11, CD13 in 10, and CD34 in seven. Four patients had one other abnormality apart from the t(6;9). These were the t(9;22) in the patient with CML and deletion 9q, addition 13q, and an isochromosome 8q in the other three patients. There were no complex karyotypes. Fms-related tyrosine kinase 3—internal tandem duplication (FLT3-ITD) mutations were seen in seven of 13 patients. Follow-up details were available for six patients. Three received palliative care, and follow-up details were not available for the other seven. The response to chemotherapy was poor in the remaining patients. The only patients who survived were three out of the four who had allogeneic hematopoietic stem cell transplantation (HSCT).

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia among adults in the Western world, with an incidence of approximately 1 out of 100,000 patients per year. CLL is characterized by the clonal expansion of immature CD5⁺ B cells. Although cytotoxic agents remain the mainstay of therapy, the disease of up to 20% of patients is not controlled with standard therapies. Therefore, there remains a need for novel therapeutic strategies. MicroRNAs (miRNAs or miRs), first identified nearly two decades ago, are noncoding RNAs that have the capacity for simultaneous regulation of tens to hundreds of genes. An association between CLL-associated chromosomal abnormalities and miRNA deregulation is beginning to emerge. miRNAs may play a biological role in the pathogenesis of CLL: specific miRNAs (miR-15a and miR-16-1) are located at a chromosomal region (13q14.3) that is often absent in patients with CLL. These same miRNAs are relevant to cellular phenotype and in vivo development of disease. This finding has led to a rapidly expanding series of investigations linking miRNAs to CLL. As a result, miRNAs are currently under investigation as diagnostic and prognostic biomarkers as well as potential therapeutic targets in CLL.