A novel subtelomeric translocation t(5;9) and a deletion of the RB1 gene in a patient with acute myeloid leukemia (AML-M0)

No chromosomal rearrangements have been identified as specifically associated with minimally differentiated acute myeloid leukemia (AML-M0). Several research groups studied the cytogenetic features of AML-M0 and found that as much as 81% of patients with AML-M0 had chromosomal rearrangements; primarily -5/5q- and/or -7/7q- deletions or translocations involving 12p. A patient, who was diagnosed with AML-M0 eighteen months ago, was referred for cytogenetic evaluation for possible AML relapse. A subtle, cryptic t(5;9)(q35.3;q34.3), plus a deletion of the RB1 gene were detected in 18 out of 20 cells analyzed by FISH utilizing the TelVysion assay kit. To rule out the possibility that these chromosomal changes were related to the relapse of AML in this case, we repeated the same FISH test on the specimen at initial diagnosis before any treatment. The same abnormalities were found. To our knowledge, this is the first case reported with subtelomeric t(5;9)(q35.3;q34.3) and the deletion of the RB1 gene in a patient with AML-M0. Whether the t(5;9) combined with the deletion of the RB1 gene plays an important role in the development of AML-M0 warrants further investigation.     

An unusual three-way translocation t(21;8;1)(q22;q22;q32) in a case of acute myeloid leukemia (M2)

Variant forms of the classic translocation t(8;21) are uncommon and account approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. These forms involve chromosomes 8, 21, and other chromosomes. Here we report a Tunisian patient with a complex rearrangement t(21;8;1)(q22;q22;q32) revealed by conventional chromosomal study at diagnosis. Fluorescence in situ hybridization study revealed the presence of the AML1-ETO chimeric gene on the derivative chromosome 8. To the best of our knowledge, this is the second case of t(21;8;1) of AML-M2 reported in the literature with the involvement of the same breakpoint at 1q32. This illustrates that this complex translocation is rarely encountered in AML and reinforces the fact that this region may harbour a critical gene candidate that may play an important role in the pathogenesis of AML. More cases are needed to elucidate its clinical features and prognosis.     

306例孕中期羊水细胞染色体核型分析

目的分析妊娠中期进行产前诊断的高危孕妇羊水细胞染色体核型,了解此期异常核型出现的频率、类型及与各种产前诊断指标的关系。方法306例有产前诊断指征的孕妇（3例为双胎妊娠）,妊娠17-24w,在B超定位下行羊膜腔穿刺术,抽取羊水细胞进行培养及染色体核型分析。结果发现异常核型16例,异常核型检出率为5.23%（16/306）。常见核型为染色体平衡易位,占异常核型的43.75%（7/16）,其中染色体相互易位6例,占异常核型的37.5%（6/16）,罗伯逊易位1例,占6.25%（1/16）;染色体三体及缺失各2例,均占12.5%（2/16）;易位型21三体及倒位各1例,均占6.25%（1/16）;染色体多态变异3例,占18.75%（3/16）。结论有各种产前诊断指征的高危孕妇中,胎儿染色体异常核型的发生率为5.23%（16/306）,染色体易位、三体、缺失及倒位是孕中期的主要染色体异常核型。     

A novel t(11;12)(q23-24;q24) in a case of minimally-differentiated acute myeloid leukemia (AML-M0)

Acute myeloid leukemia with minimal signs of myeloid differentiation (AML-M0) is a recent addition to the FAB group classification. Chromosome data is scarce, but existing reports describe a high incidence of complex karyotypes and myelodysplastic syndrome-like chromosome alterations, while single chromosome translocations have rarely been reported. We describe the case of a 60-year-old woman diagnosed with AML-M0 with a novel translocation t(11;12)(q23-24;q24) as the sole karyotypic marker. Fluorescence in situ hybridization analysis to assess MLL gene splitting did not show rearrangement of this oncogene.     

评价羊水染色体检测在产前诊断中的作用

目的评价羊水细胞染色体检测在产前诊断中的作用。方法对妊娠16∽24w的孕妇939例进行羊膜腔穿刺术,对羊水细胞染色体分析。结果检测出染色体异常共54例,其中21-三体13例,18-三体1例,13-三体1例,性染色体异常9例,平衡易位14例,其他染色体结构异常16例。结论羊水染色体检测可安全、有效的检测胎儿染色体异常,具有重要意义,值得进一步推广。     

Unique insertional translocation in a childhood Wilms' tumor survivor detected when his daughter developed bilateral retinoblastoma

Retinoblastoma and Wilms' tumor are rare childhood embryonic tumors associated with loss or inactivation of tumor suppressor genes, RB1 located within 13q14, and WT1 located within 11p13. Interchromosomal insertional translocations occur rarely, and such rearrangements within RB1 or WT1, even rarer. We report a unique family in which an insertional translocation of a chromosomal segment that included band 13q14 inserted into 11p13 caused childhood Wilms' tumor in the father, and whose child developed bilateral retinoblastoma. This is the first case of an insertional translocation that caused both tumors. This insertional translocation had significant consequences for genetic counseling and in utero diagnosis. The estimated risk for an offspring of this father to develop Wilms' tumor is up to 50%, to develop retinoblastoma up to 25%, to have neither tumor 25%, and to have both tumors 0%.     

An uncommon case of de novo CD10+ CD5? mantle cell lymphoma mimics follicle center B cell lymphoma

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by expression of CD5, overexpres-sion of Cyclin D1 as a result of chromosomal translocation t(11;14)(q13;q32), and poor prognosis. Cases of MCL lacking CD5 expression as well as cases with coexpression of CD5 and CD10 have also been reported. Here we describe an uncommon case of de novo MCL with expression of CD10, but not CD5, mimicking lymphoma of germinal center-derived B cells. The lymphoma cells in this case demonstrated a diffuse pattern of proliferation, and were strongly positive for Cyclin D1 by immunohistochemical stain. Fluorescence in situ hybridization studies demonstrated the presence of t(11;14)(q13;q32) involving BCL1, but not chromosomal translocations involving C-MYC or BCL2, confirming the diagnosis of MCL. This case further highlights the importance of comprehensive immunopheno-typic and genetic characterization in the diagnosis and classification of B-cell lymphomas.     

A case of follicular small cleaved cell lymphoma with t(14;18) and t(8;11)

Follicular small cleaved cell lymphoma is a common B-cell lymphoma exhibiting a t(14;18)(q32;q21) chromosomal translocation, which has been found in most cases studied. In our case of follicular small cleaved cell lymphoma, the chromosome translocation 14;18 was observed. This case also exhibits a second consistent chromosomal translocation, t(8;11)(p21;q13), along with t(14;18).     

Banding and molecular cytogenetic studies detected a CBFB-MYH11 fusion gene that appeared as abnormal chromosomes 1 and 16 in a baby with acute myeloid leukemia FAB M4-Eo

The acute myeloid leukemia (AML) subtype M4Eo occurs in 5% of all AML cases and is usually associated with either an inv(16)(p13.1q22) or a t(16;16)(p13.1;q22) chromosomal abnormality. At the molecular level, these abnormalities generate a CBFB-MYH11 fusion gene. Patients with this genetic alteration are usually assigned to a low-risk group and thus receive standard chemotherapy. AML-M4Eo is rarely found in infants. We describe clinical, conventional banding, and molecular cytogenetic data for a 12-month-old baby with AML-M4Eo and a chimeric CBFB-MYH11 fusion gene masked by a novel rearrangement between chromosomes 1 and 16. This rearrangement characterizes a new type of inv(16)(p13.1q22) masked by a chromosome translocation.     

Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.     

Detection of t(12;14)(p13;q32) in a patient with IGH-CCND1 negative mantle cell lymphoma resembling ultra-high risk chronic lymphocytic leukemia

t(12;14)(p13;q32) is a rare recurrent chromosomal translocation, which has only been identified in a small subgroup of mantle cell lymphoma (MCL) without typical t(11;14)(q13;q32). This rearrangement causes aberrant over-expression of cyclin D2 (CCND2), which disrupts the normal cell cycle. Here we report a subtle case of MCL with t(12;14)(p13;q32) that was initially misdiagnosed as ultra-high risk chronic lymphocytic leukemia (CLL). A 60-year-old male patient presented with obvious leukocytosis and progressive weakness. Morphology of peripheral blood and immunophenotyping by flow cytometry pointed to a diagnosis of chronic lymphocytic leukemia. Fluorescence in situ hybridization (FISH) using IGH-CCND1 probe was negative for CCND1 abnormality, but demonstrated IGH breakapart signals. The initial diagnosis of CLL was established and the patient was treated with six courses of immunochemotherpy with fludarabine, cyclophosphamide and rituximab (FCR). Complete remission (CR) was achieved at the end of treatment, but disease relapsed quickly. The patient was transferred to our hospital, flow cytometry using additional markers showed that the clonal cells were CD200+(dim), CD148+(strong), and chromosome analysis revealed a complex karyotype, 47, XY, t(12;14)(p13;q32), +12, del(9p21), which indicated over-expression of CCND2, and immunostaining showed strong positivity of SOX11 further confirming the characteristics of CCND1-negtive MCL. The final diagnosis was revised to rare subtype of MCL with CCND2 translocation and intensive regimens were employed. This confusable MCL case illustrates the importance of cytogenetic analysis and clinicopathologic diagnosis of this rare category of MCL.     

Activation of HLXB9 by juxtaposition with MYB via formation of t(6;7)(q23;q36) in an AML-M4 cell line (GDM-1)

Mutation or dysregulation of related homeobox genes occurs in leukemia. Using RT-PCR, we screened members of the EHG family of homeobox genes, comprising EN1 (at 2q14), GBX2 (at 2q36), and EN2, GBX1, and HLXB9 (at 7q36), for dysregulation in acute myeloid leukemia (AML) cell lines indicated by chromosomal breakpoints at these sites. Only one EHG-family gene was expressed, HLXB9, in cell line GDM-1 (AML-M4). Karyotypic analysis of GDM-1 revealed a unique t(6;7)(q23;q35), also present in the patient. Fluorescence in situ hybridization analysis showed chromosomal breakpoints close to the region upstream of HLXB9, at 7q36, a region rearranged in certain AML patients, and at 6q23 upstream of MYB, a gene activated in leukemia. Detailed expression analysis suggested ectopic activation of HLXB9 occurred via juxtaposition with regions upstream of MYB, which was highly expressed in GDM-1. Our data identified a cell line model for a novel leukemic translocation involving MYB with HLXB9, further implicating HLXB9 in leukemogenesis.     

176例超声诊断结构异常胎儿的脐血染色体核型分析

目的探讨对超声诊断结构异常胎儿进行脐血染色体核型分析的意义。方法选择我院因产前超声诊断胎儿结构异常而自愿行介入性产前诊断的孕妇176例,行脐静脉穿刺,分析脐血细胞染色体核型。结果脐静脉穿刺成功率为98.86%,脐血细胞培养率为100%。确诊染色体异常胎儿18例（10.23%）,其中21-三体综合征6例,18-三体综合征7例,13-三体综合征2例,Turner综合征1例,三体征1例,染色体易位1例。结论对超声诊断结构异常胎儿进行介入性产前诊断,可以明确是否为染色体异常疾病,有重要的临床意义;脐静脉穿刺因其对母儿风险小,操作简便,且不受妊娠时间的限制而具有重要意义。     

Diphallus and associated anomalies with balanced autosomal chromosomal translocation

We report a sporadic case of complete diphallus with multiple other anomalies in a premature newborn. Chromosomal analysis at the 500 band level showed an apparently balanced reciprocal translocation 46,XY, t(1;14)(p36.3;q24.3). The mother has a normal karyotype, but the father was not available for chromosomal analysis. The significance of this balanced chromosomal rearrangement and the possibility that the chromosomal breakpoints contribute to deregulation of mesodermal development is discussed.     

Clonal chromosome abnormalities in a plexiform cellular schwannoma

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, accounting for 5%-8% of all pediatric malignancies. RMS can be categorized into several subtypes, including embryonal RMS (ERMS), the botryoid and spindle cell variants of ERMS, and alveolar RMS (ARMS). The t(2;13)(q35;q14) and the variant t(1;13)(p36;q14) are seen in a majority of ARMS cases. In contrast, the embryonal subtype of rhabdomyosarcoma has not been associated with a recurring chromosomal translocation. We describe here a novel chromosomal t(2;20)(q35;p12) occurring in a case of childhood RMS with embryonal histology. It is notable that this translocation harbors breakpoints at or near the locus of the PAX3 gene, which is involved in the most common recurring translocation associated with ARMS.     

Burkitt lymphoma with dual translocation of chromosome 14: a novel chromosomal abnormality of t(8;14),t(14;15)

Burkitt lymphomas (BLs) frequently show secondary chromosomal abnormalities. Here, the authors describe a case of BL with an unusual dual translocation of chromosome 14, t(8;14) and t(14;15), and partial duplication of 1q. This 5-yr-old female patient had several unfavorable prognostic factors including elevated serum lactate dehydrogenase activity and involvement of the central nervous system and bone marrow. Despite receiving CCG-106A chemotherapy, she was resistant to therapy and died on the 70th hospital day. To our knowledge, this is the first documented case report of BL harboring dual translocation of chromosome 14 involving chromosomes 8 and 15, which may be a factor associated with unfavorable clinical course.     

Translocation t(13;14) in nine generations with a case of translocation homozygosity

The Robertsonian translocation 5(13;14)(p11;q11) was studied in three families with probable common ancestry in Eastern Finland. In the largest family the translocation has segregated through at least nine generations. The same family also included a female who was homozygous for t(13;14). No clear-cut effect of the translocation on fertility could be demonstrated and only one case of trisomy 13 was recorded in the offspring of t(13;14) carriers. The results are discussed, with implication for human chromosomal evolution.     

bcl-1 REARRANGEMENT AND CYCLIN D1 PROTEIN EXPRESSION IN MANTLE CELL LYMPHOMA

Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1–S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas ( n =40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL.