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Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic characterization of a new case with analphoid NMC derived from 15q25-->qter using high-resolution comparative genomic hybridization (HR-CGH) and multiplex fluorescence in situ hybridization analyses with various alpha-satellite DNA probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months, showed accelerated growth, partial deafness, and a phenotype similar to that of the eight previously reported cases of distal 15q tetrasomy. Chromosome studies showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA polymorphism study demonstrated that this extra SMC is an NMC containing an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25-->qter) which originated paternally, i.e. ish der(15)(qte-->q25::q25[neocen]-->qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the phenotype related to tetrasomy of this specific chromosome segment and represents a new report of a neocentromere on distal chromosome 15q suggesting that this region appears to be susceptible to the formation of neocentromeres.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic characterization of a new case with analphoid NMC derived from 15q25--qter using high-resolution comparative genomic hybridization (HR-CGH) and multiplex fluorescence in situ hybridization analyses with various alpha-satellite DNA probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months, showed accelerated growth, partial deafness, and a phenotype similar to that of the eight previously reported cases of distal 15q tetrasomy. Chromosome studies showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA polymorphism study demonstrated that this extra SMC is an NMC containing an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25--qter) which originated paternally, i.e. ish der(15)(qte--q25::q25[neocen]--qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the phenotype related to tetrasomy of this specific chromosome segment and represents a new report of a neocentromere on distal chromosome 15q suggesting that this region appears to be susceptible to the formation of neocentromeres.

Ovarian cancer is the leading cause of death from gynecologic malignancy among women in the United States. In 1997, there were nearly 27,000 ovarian cancer cases with over 14,000 deaths. Recent attempts at early detection of ovarian cancer have been aimed at the identification of biomarkers that would indicate an underlining malignant process or reflect the biological behavior of the tumor. Our previous studies revealed that chromosome 8 copy number abnormality, especially trisomy, is common in several cancers. Archival tissues from 24 cases of papillary serous ovarian carcinoma (10 stage I and 14 stage III) were analyzed by FISH with a chromsome 8 α-satellite probe (Oncor, Gaithersburg, MD). The analysis was done according to standard protocols of the Lifespan Academic Medical Center Cytogenetics Laboratory at Rhode Island Hospital. Twenty-one out of 24 cases (87.5%) were found to be trisomic for chromosome 8, if a cutoff point of ≥15% cells with three signals is adopted. Overall 80% of stage I and 93% of stage III tumors had trisomy 8. This study confirms the presence of a high frequency of trisomy 8 in both early and late stages of the disease and suggests that trisomy 8 may be an early event in the multi-step process leading to ovarian cancer. (This study was funded in part by Vysis, Inc., Downers Grove, IL.)

We describe a 38-year-old man with a chronic myeloproliferative syndrome characterized by elevated white blood cell and platelet counts and increased blasts in the peripheral blood. Bone marrow aspiration was a "dry tap" and the biopsy specimen was hypercellular with numerous blasts, atypical megakaryocytes, and increased reticulin fibrosis. The blasts exhibited cytochemical reactivity for nonspecific esterase and PAS and immunohistochemically were positive for factor VIII, supporting megakaryoblastic lineage. Cytogenetic studies of peripheral blood revealed the t(9;22)(q34;q11). We interpreted these findings to be most consistent with chronic myeloid leukemia (CML) manifested at the time of megakaryoblastic crisis. Although the initial complete blood count showed leukocytosis and thrombocytosis, the patient subsequently had pancytopenia with clinical and pathologic findings consistent with acute myelofibrosis (AMF). Cytosine arabinoside and etoposide chemotherapy induced remission of the acute leukemia. We conclude that CML infrequently presents itself in megakaryoblastic crisis and that such cases may result in the clinicopathologic syndrome of AMF. The success of chemotherapy in this case also suggests that intensive antileukemic therapy may be useful in other patients with either CML-blast crisis or the clinicopathologic syndrome of AMF.