TPA stimulation culture for improved detection of t(11;14)(q13;q32) in mantle cell lymphoma

Cytogenetic analysis of mantle cell lymphoma (MCL), characterized by the presence of t(11;14)(q13;q32) translocation, is often difficult because of the low proliferating rate of MCL cells and the presence of normal cells in bone marrow which may interfere with growth of MCL cells. We describe herein a TPA (12-O-tetradecanoylphorbol 13-acetate) stimulated culture to improve detection of t(11;14)(q13;q32) in 20 MCL patients regardless of the samples used.     

The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma

Summary The T cell receptor chain gene locus and the immunoglobulin heavy chain gene locus (IgH) have previously been mapped to the q11 and q32 positions respectively of the human chromosome 14. Both of these sites are also common breakpoints in lymphocytes from ataxia telangiectasia (A-T) patients. Using in situ hybridisation we show that the 14q32 breakpoint in an A-t non-leukaemic T cell clone with t(14;14) translocation, lies outside the IgH locus and proximal to it with respect to the centromere. The 14q11-14qter segment of the homologous chromosome 14 carrying the constant gene region of the chain locus is translocated to this 14q32 position.     

A subpopulation of t(2;14)(p11;q32) cells in ataxia telangiectasia B lymphocytes

Summary Partially purified B cells from ataxia telangiectasia (A-T) patients and normal individuals were stimulated with Staphylococcus aureus Cowan I organisms (SAC). High levels of apparently random rearrangements were seen in the A-T B cells only. In addition a t(2;14)(p11;q32) rearrangement was identified in B cells from more than one patient.     

Trisomy 16q13→qter in a infant from a t (11;16)(q25;q13) translocation-carrier father

Summary A female infant with 16q trisomy resulting from a paternally inherited balanced translocation is described and compared with five previously reported cases. All the babies were of low birth weight and expired within 1 year, with only one exception. Necropsy of the present case revealed atrial septal defect, single left lobe of the lung, anomalous lobulation of the liver, agenesis of the gall bladder, and anovestibular fistula.     

The gene that encodes the human CD20 (B1) differentiation antigen is located on chromosome 11 near the t(11;14)(q13;q32) translocation site

The human CD20 gene (B1) encodes a B lymphocyte-specific, cell-surface molecule that is involved in B cell activation and differentiation. We report that the CD20 gene is located on human chromosome 11 at position q12-q13. The location of CD20 was determined by in situ hybridization and was further confirmed by Southern blot analysis of DNA from rodent/human hybrids that contained only portions of human chromosome 11. This localization places the CD20 gene near the site of the t(11;14)(q13;q32) translocation that is found in a subgroup of B cell-lineage malignancies. The site of this translocation has been previously identified by DNA cloning and termed bcl-1. The CD20 gene was found to lie on the centromeric side of bcl-1 on chromosome 11 and to be separated from bcl-1 by at least 50 kb of DNA. These results raise the possibility that alterations in the expression of the CD20 gene may result after the t(11;14) chromosomal alteration.     

Translocation t(11;14) and trisomy 11q13----qter in multiple myeloma

A 14q+ marker with extra material derived from chromosome 11 long arm, i.e. segment q13----qter, has been found in cells from a pleural effusion in a patient with highly malignant multiple myeloma. The segment 11q13----qter was trisomic because of the presence of both apparently normal homologous chromosomes 11.     

Trisomy 20pter»q11 in a malformed boy from a t(13;20)(p11;q11) translocation-carrier mother

Summary A 31-year-old boy revealed moderate motor and mental retardation, normal growth, a congenital heart defect and multiple minor dysmorphic signs and anomalies including brachycephaly, orbital hypotelorism, upward slanting palpebral fissures, short and beaked nose, full cheeks, malformed auricles, hypoplastic external genitalia, rocker-bottom feet with prominent heels, and various minor radiologic anomalies of bones. An extra chromosome in his karyotype appeared to represent trisomy of the short arm of chromosome 20 due to a maternally inherited balanced t(13;20)(p11;q11) translocation.     

Partial trisomy 14q due to maternal t(4;14)(p16;q32) in a dysmorphic newborn

Partial Trisomy 14q is a rare chromosomal disorder that mostly results from a parental translocation. We report here a newborn boy with partial trisomy 14q and dysmorphic features that are compatible with previously reported cases. Conventional cytogenetic analysis revealed an extra chromosomal segment at the end of the short arm of chromosome 4. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of these cytogenetic studies and the physical examination, this dysmorphic case was diagnosed as partial trisomy of 14q and his karyotype determined as 46 XY, der(4)t(4;14)(p16;q32) resulting from a balanced maternal translocation identified as 46,XX, t(4;14)(p16;q32).     

Different breakage-prone regions on chromosome 1 detected in t(11;14)-positive mantle cell lymphoma cell lines and multiple myeloma cell lines are associated with different tumor progression-related mechanisms

To better define secondary aberrations that occur in addition to translocation t(11;14)(q13;q32) in mantle cell lymphomas (MCL) and in multiple myelomas (MM), seven t(11;14)-positive MCL cell lines and four t(11;14)-positive MM cell lines were analysed by fluorescence R-banding and spectral karyotyping (SKY). Compared with published data obtained by G-banding, most chromosome aberrations were redefined or further specified. Furthermore, several additional chromosome aberrations were identified. Thus, these cytogenetically well defined t(11;14)-positive MCL and MM cell lines may be useful tools for the identification and characterization of genes that might be involved in the pathogenesis of MCL and MM, respectively. Since MCL and MM were found to have different alterations of chromosome 1, these were investigated in more detail by fluorescence in situ hybridization (FISH) and multicolor banding (MCB) analyses. The most frequently altered and deletion-prone loci in MCL cell lines were regions 1p31 and 1p21. In contrast, breakpoints in MM cell lines most often involved the heterochromatic regions 1p12-->p11, and the subcentromeric regions 1q12 and 1q21. These data are in accordance with previously published data of primary lymphomas. Our findings may indicate that different pathways of clonal evolution are involved in these morphologically distinct lymphomas harboring an identical primary chromosome aberration, t(11;14).     

Unbalanced 1q whole-arm translocation resulting in der(14)t(1;14)(q11-12;p11) in myelodysplastic syndrome

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.     

Partial trisomy 18(q11 leads to qter) in an infant and aborted fetus resulting from a balanced paternal translocation t(13;18)(q32:q11).

Partial trisomy 18 is described in a two month old female with severe mental, motor and growth retardation, associated with multiple congenital anomalies characteristic of complete trisomy 18. Trisomy for almost all of 18q resulted from adjacent I segregation of a paternally inherited translocation t(13; 18)(q32:q11). The balanced translocation was observed in three generations of the family. Partial trisomy 18q identical to that observed in the proband was found in a subsequent miscarriage.     

Fine mapping of the constitutional translocation t(11;22)(q23;q11)

Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal translocation in man. Balanced carriers are phenotypically normal, except for decreased fertility, an increased spontaneous abortion rate and a possible predisposition to breast cancer in some families. Here, we report the high resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC) clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a variation of the breakpoint position between patients. In 22q11, we have sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region; these contain low copy repeats (LCRs). Southern blot analysis with probes from BAC2280L11 has revealed different patterns between normal controls and translocation carriers, indicating that sequences similar/identical to these probes flank the translocation breakpoint. The occurrence of LCRs has previously been associated with genomic instability and "unclonable" regions. Hence, the presence of such repeats renders standard translocation breakpoint cloning techniques ineffective. Thus, we have used high resolution fiber-FISH to study this region in normal and translocation cases by using probes from 22q11, LCRs and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we have localised the breakpoint in 22q11 to approximately 20-40 kb from the centromeric border of the LCR (i.e. the telomeric end of AC006547) and have confirmed the breakpoint position on 11q23.     

Familial aniridia and translocation t(4;11)(q22;p13) without Wilms' tumor

A family with dominantly inherited aniridia in three generations is presented. All three patients had an apparently balanced chromosome translocation t(4;11)(q22;p13). The patients were otherwise clinically normal and without signs of Wilms' tumor; their erythrocyte catalase activities were within the normal range. We suggest that in this family aniridia is caused either by a submicroscopic deletion at the translocation breakpoint 11p13 or by a position effect on the same chromosome segment. Furthermore, the loci for aniridia and Wilms' tumor susceptibility are separate. It follows that the WAGR complex is caused by a mutation of more than one gene located at 11p13. The theoretical implications of a presumably defective allele causing a mendelian dominant phenotype are discussed.     

47,XY,+der(11;22)(q23;q12) following balanced translocation t(11;22)(q23;q12)mat

Summary Report of a supernumerary extra chromosome der(11;22)(q23; q12) resulting from a balanced translocation in the mother. The propositus suffers from mental deficiency, deafness and extreme muscular weakness and exhibits cleft palate, a labial lymphangioma and an atrial septum defect. Since the features of partial trisomy 11q23 frequently associated with a translocation t(11q;22q) bear similarities with the cases of so called trisomy 22 one might conjecture that some of these observations are in fact products of translocations including partial 11q.     

Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia

Molecular analysis of somatic cell hybrids derived from T cells carrying a t(7;14)(q35;q32) chromosomal translocation from a patient with ataxia telangiectasia and T cell leukemia indicates that the breakpoint on chromosome 14 is proximal to the IgH locus and to the D14S1 locus, while the breakpoint on chromosome 7 involves the T cell receptor beta chain locus immediately 5' to J beta 1.5 on chromosome 7. The separation of V beta and C beta observed in somatic cell hybrids defined the orientation of the T cell receptor beta chain locus on chromosome 7 where the V beta genes are centromeric and the C beta genes are telomeric. A novel chromosomal alteration, undetected cytogenetically, was revealed as being an inversion with duplication of the distal band of chromosome 14q32. The importance of the 14q32 region in the leukemogenic process is discussed.     

Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome

Summary Leukocyte peroxidase activity was estimated in 5 patients with the juvenile form of neuronal ceroid lipofuscinosis (Spielmeyer-Vogt's disease) and in 15 healthy controls. In contradiction to recent reports normal activity of p-phenylene diamine mediated peroxidase was found in the patients. The possible role of contamination of the white cell preparation with hemoglobin is discussed.     

An azoospermic male with reciprocal translocation t(1;15)(q11;p11)

Summary The authors report on a case of 1;15 translocation and request contact with any colleagues who have observed similar cases.