Chromosomal translocation t(1;13)(p36;q14) in a case of rhabdomyosarcoma.

Cytogenetic studies of a rhabdomyosarcoma of mixed embryonal and alveolar histology in an 11-month-old male revealed a single structural abnormality, t(1;13)(p36;q14). This abnormality may define a subset of patients with a variant of the t(2;13)(q35;q14) translocation frequently seen in alveolar rhabdomyosarcoma.     

Solid alveolar rhabdomyosarcoma with a t(2;13)

We report a child with a progressive “solid alveolar rhabdomyosarcoma” in whom analysis of tumor cells revealed a t(2;13) translocation characteristic of the classical alveolar subtype. Both subtypes of alveolar rhabdomyosarcoma are associated with a poor response to treatment and the occurrence of this translocation in both is suggestive of a common biologic origin.     

Paternal Robertsonian translocation t(13q;14q) and maternal reciprocal translocation t(7p;13q) in a couple with repeated fetal loss.

Marriages involving partners both of whom have abnormal karyotypes are rare and are usually ascertained because of a history of infertility, repeated abortions, or the birth of a balanced translocation carrier or chromosomally abnormal offspring. Abnormalities which have been noted include sex chromosome aberrations in both parents or a sex chromosome abnormality in one parent and an autosomal abnormality in the other. Four papers have reported balanced reciprocal autosomal translocations in both parents, two couples representing a first cousin marriage. We present a case of a paternal 13;14 Robertsonian translocation and a maternal (7p;13q) reciprocal translocation in a couple with repeated fetal loss.     

A familial chromosomal translocation t(6q;7q) with habitual abortions

A familial balanced translocation between the long arms of chromosomes 6 and 7 is described. The break points are localized to 6q27 and 7q23. No phenotypical abnormalities were found in any of the three carriers, but spontaneous abortions were frequent and might be associated with the translocation due to unbalanced segregation.     

Alveolar rhabdomyosarcoma with del(13q14)

We report a case of disseminated alveolar rhabdomyosarcoma, where chromosome analysis showed a deletion of chromosome 13(q14). This breakpoint is involved in the t(2;13)(q37;q14) previously reported in cases of rhabdomyosarcoma, but this is the first reported case in whom this deletion occurs without involvement of chromosome 2. The possible oncogenic role of the retinoblastoma (RB1) gene located at the breakpoint is discussed.     

Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma

We present cytogenetic and molecular genetic analyses of two cases of alveolar rhabdomyosarcoma. The characteristic translocation between chromosomes 2 and 13, t(2;13)(q35;q14), has been identified in both cases. Using cell lines derived from these tumor specimens, we have performed Southern blot analysis to investigate the possibility of rearrangement of 14 candidate genes mapping to the relevant regions of 2q and 13q. These candidate genes can be divided into 5 groups: signal transduction proteins (RB1, inhibin alpha, FLT1, and HOX4B), muscle-specific products [myosin light chain, desmin, and nicotinic cholinergic receptor subunits gamma and delta (CHRNG and CHRND)], extracellular matrix proteins (collagen type VI alpha 3 chain, elastin, and fibronectin), transformation-associated products (intestinal alkaline phosphatase and L-plastin), and other genes (esterase D). Conventional gel electrophoresis followed by Southern blot analysis indicated no evidence of rearrangement within or near these genes except for a rearrangement in the CHRNG-CHRND locus, which occurred only in a subpopulation of the late recurrence tumor cells of one patient. In addition, we employed pulsed-field gel electrophoresis-Southern blot analysis to demonstrate the absence of detectable rearrangements within a larger region around each of these genes.     

A variant (2;13) translocation in rhabdomyosarcoma

Cytogenetic analysis of a right buttock mass from a 5-year-old boy showed translocation between an inverted chromosome 1 and a chromosome 13 as the sole cytogenetic abnormality. The breakpoint 13q14 appears to be the same as in previously reported cases of rhabdomyosarcoma (mostly of the alveolar type), but does not show involvement of 2q37. We suggest that this translocation may be a variant of the classical t(2;13)(q37;q14) found in rhabdomyosarcoma.     

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.     

Detection of the t(2;13)(q35;q14) and PAX3-FKHR fusion in alveolar rhabdomyosarcoma by fluorescence in situ hybridization

Cytogenetic studies of the pediatric solid tumor alveolar rhabdomyosarcoma have demonstrated the presence of a consistent chromosomal translocation, t(2;13)(q35;q14). We recently identified PAX3 and FKHR as the genes on chromosomes 2 and 13, respectively, that are juxtaposed by this translocation. As one means of detecting the t(2;13) translocation in clinical specimens, we have developed a fluorescence in situ hybridization (FISH) assay that may be used for both interphase and metaphase cells. Translocation of the 5′ region of the FKHR gene to the derivative chromosome 2, and retention of the 3′ region of FKHR on the derivative chromosome 13 [(der(13)], were demonstrated in metaphase cells from a rhabdomyosarcoma cell line with a previously identified t(2;13) translocation. A 5′ PAX3 cosmid probe was shown to localize to 2q35 in normal cells, and to translocate to the der(13) in the rhabdomyosarcoma cell line. In order to detect the der(13) in interphase nuclei, we labeled the 3′FKHR and the 5′PAX3 cosmid probes with digoxigenin and biotin, respectively, and used these in a two-color FISH assay. The presence of the der(13) was visualized as juxtaposed or overlapping red and green signals in metaphase and interphase tumor cells. The PAX3-FKHR FISH assay was then applied to a series of cytogenetically characterized pediatric sarcoma cell lines. The presence of the der(13) was demonstrated by FISH in all cases containing a cytogenetically detectable t(2;13). The FISH assay was then applied to a series of 20 embryonal and alveolar rhabdomyosarcoma samples. All 10 of the alveolar rhabdomyosarcoma specimens demonstrated a der(13) with the FISH assay. We did not detect a PAX3-FKHR fusion in 10 embryonal rhabdomyosarcoma cases. Thus, the two-color FISH assay is a sensitive and rapid means of identifying the t(2;13) in rhabdomyosarcoma specimens, and it will be a useful adjunct for the diagnosis of pediatric small round cell tumors. The cosmid probes for the 5′ and 3′ regions of FKHR, as well as the probe for PAX3, will be useful for molecular cytogenetic studies of variant translocations in rhabdomyosarcoma, such as the t(1;13)(p36;q14).     

Derivative (14)t(11;14)(q13;q32)t(11;14)(p11.2;p11.2): a novel unbalanced variant of the t(11;14)(q13;q32) translocation in mantle cell lymphoma

We report the case of a 62-year-old man who presented with splenomegaly, leukocytosis, anemia, and thrombocytopenia. Examination of the peripheral blood, bone marrow, and spleen revealed involvement by mantle cell lymphoma, with some blastoid features and an atypical phenotype. Spleen and bone marrow classical chromosome analysis followed by fluorescence in situ hybridization revealed a novel and unusual unbalanced variant of the t(11;14)(q13;q32) translocation, resulting in a complex derivative chromosome harboring the IGH/CCND1 fusion gene. This chromosome was designated as der(14)t(11;14)(q13;q32)t(11;14)(p11.1;p11.2).     

A case of rhabdomyosarcoma of the bladder with a (2;5) chromosomal translocation in peripheral lymphocytes

Chromosome analysis was performed on peripheral blood lymphocytes of a patient with rhabdomyosarcoma of the urinary bladder. It showed a reciprocal t(2;5) translocation with the breakpoints at 2q37.3 and 5q31.3. This is the first report of such an anomaly in the peripheral lymphocytes of a patient with rhabdomyosarcoma of the urinary bladder.     

Familial D/D translocation t(13q;14q) Eight members in four generations

Eight family members spanning four generations were found to have 45 chromosome count D/D translocation identified by Giemsa-trypsin banding as t(13q;14q). The only mature male is believed to be infertile on the basis of a very low sperm count with reduced motility. This is believed to be related to the chromosome aberration and not to be coincidental. Aside from this, all were clinically normal except the index case, a young girl with unusual facies and moderate to severe retardation of growth and development. It is believed that her abnormalities were coincidental to the chromosome translocation and fortuitous in locating this family and initiating the pedigree. This example of essentially benign (some males are fertile) Robertsonian centric fusion in humans lends itself to interesting speculations about the results from chance matings between such translocation carriers.     

Molecular cloning of a t(11; 14)(q13;q32) translocation breakpoint centromeric to the BCLI-MTC

In B-cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCLI locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCLI major translocation cluster (MTC) and the PRADI (also termed cyclin DI or CCNDI) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRADI. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHOII_c) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCLI locus. Rearrangements in the BCLI locus are associated with deregulation of the PRADI gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRADI expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCLI locus boundaries. We think that attention should be focused on this region centromeric to the BCLI-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRADI gene deregulation in t(11;14) associated pathologies.     

Solid variant of alveolar rhabdomyosarcoma with unbalanced t(2;13) and hypotetraploidy, without MYCN amplification

The histological subtype of alveolar rhabdomyosarcoma (AR) is characterised by the cytogenetic translocation t(2;13)(q35;q14) in approximately 70% of cases, a rearrangement rarely present in the embryonal rhabdomyosarcoma (ER) subtype. The MYCN gene is amplified in some cases of AR. We present a young man with an unusual pattern, namely solid variant of AR with hypotetraploidy and the t(2;13) in an unbalanced form. The MYCN gene was not amplified on FISH, but showed increased copy number, consistent with ploidy.     

t(14;19)(q32;q13): a recurrent translocation in B-cell precursor acute lymphoblastic leukemia

The recurrent t(14;19)(q32;q13) translocation associated with chronic B-cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B-cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus-specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)-positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B-cell precursor acute lymphoblastic leukemia.     

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.