Genes, Chromosomes and Cancer

doi: 10.1002/gcc.2870040301pmid: N/A

Kees, Ursula R.; Ford, Jette; Willoughby, Michael L. N.; Rudduck, Christina; Margaret Garson, O.; Spagnolo, Dominic; Papadimitriou, John

doi: 10.1002/gcc.2870040302pmid: 1382559

A 6‐year‐old girl presented with a tumor of the right shoulder involving bone, adjacent soft tissue, and regional lymph nodes. The conventional histologic diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma therapy, reevaluation with additional multiple diagnostic techniques performed on the biopsy tissue and on two cell lines derived from the biopsies established the diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was strongly supported by 1) focal rosette formation by the tumor cells and positive immunostaining for neuron‐specific enolase and synaptophysin, with absent staining for leukocyte common antigen; 2) at the ultrastructural level, formation of cellular processes containing microtubules, a paucity of neurosecretory granules, absence of synaptic junctions, formation of long “intermediate” junctions between cells, and, in culture, widespread development of rosettes; 3) marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4) elevated expression of MYC and lack of overexpression of MYCN oncogenes. Numerical and structural abnormalities were present in the karyotype, but the expected t(11;22)(q24;q12) was not present in the tumorinvolved marrow or in either of the established tumor cell lines, although there was an interstitial deletion of 11q involving breakpoints in q21 and q23.

Gargano, Silvia; Caporossi, Daniela; Gualandi, Giampiero; Calef, Enrico

doi: 10.1002/gcc.2870040303pmid: 1382560

The Epstein‐Barr virus genome contained in the Burkitt lymphoma line Namalwa was previously localized to the short arm of chromosome I. Analysis of a different subline of the same Namalwa line by means of Southern analysis carried out on genomic DNA, as well as in situ hybridization, showed a localization on the X chromosome.

Xia, Ying; Brown, Lamorna; Tsan, Julia Tsou; Chuan‐Yang, Cary Ying; Baer, Richard; Siciliano, Michael J.; Crist, William M.; Carroll, Andrew J.

doi: 10.1002/gcc.2870040304pmid: 1382561

Nearly 30 percent of patients with T‐cell acute lymphoblastic leukemia (T‐ALL) exhibit a tumor‐specific rearrangement of the TAL1 gene (also called TCL5 or SCL). These rearrangements are generated by either local DNA deletion or a (1;14)(p34;q11) chromosome translocation, and they typically result in structural alterations of the TAL1 transcription unit. In this report we present a molecular characterization of the t(1;14)(p34;q11) from a T‐ALL patient. As a consequence of the translocation, TAL1 is transposed from its normal position on chromosome 1 into the T‐cell receptor α/δ chain locus on chromosome 14. Unlike previous cases, the chromosome 1 breakpoint in this patient did not disrupt the continuity of the TAL1 transcription unit, but instead occurred approximately 25 kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant alteration of TAL1 can be mediated by long‐range cis‐activating mechanisms that are triggered by DNA rearrangement at a distant site.

Horsthemke, Barnhard; Prescher, Gabriele; Becher, Reinhard; Bornfeld, Norbert

doi: 10.1002/gcc.2870040305pmid: 1382562

Uveal melanoma is the most frequent primary intraocular tumor. The etiology is unknown. Using neutral DNA polymorphisms on chromosomes 2, 3, and 8, we have detected loss of chromosome 3 alleles in 8 of 13 tumors and multiplication of chromosome 8 alleles in 6 of 11 tumors. No anomalies at a locus on chromosome 2 were found in 10 of 10 tumors. These results confirm and extend previous cytogenetic findings and suggest that a tumor suppressor gene on chromosome 3 and an oncogene on chromosome 8 may be involved in the formation or progression of this tumor.

Lorber, Briana J.; Freeman, Sallie B.; Hassold, Terry; Ragab, Abdel H.; Vega, Roger A.; Cockwell, Annette E.; Jacobs, Patricia A.; Radford, Martin; Doyle, John; Dubé, Ian D.; Zipursky, Alvin

doi: 10.1002/gcc.2870040306

Heppell‐Parton, Amanda C.; Rabbitts, Pamela H.; Albertson, Donna G.

doi: 10.1002/gcc.2870040307pmid: 1382564

Using fluorescence in situ hybridisation (FISH) the chromosomal location and relative order of six human chromosome 3 probes has been determined. The sensitivity of the technique has enabled the relative mapping of probes carrying inserts as small as 500 basepairs (bp), thus allowing the following proximal–distal probe order to be proposed: D3S30 (3p13–14), D3S4 (3p13–14), D3S2 (distal 3p14), D3S32 (3p21), D3S48E (3p21–23), and D3S11 (3p22–23). These data combined with the deletion mapping data of other researchers raise the possibility that the loss of more than one region of the short arm of chromosome 3 may be important in the development of small cell lung cancer.

Mertens, Fredrik; Jin, Yuesheng; Heim, Sverre; Mandahl, Nils; Mitelman, Felix; Jonsson, Nils; Persson, Bertil; Wennerberg, Johan; Mertens, Ove; Salemark, Lars

doi: 10.1002/gcc.2870040308pmid: 1382565

Shapiro, David N.; Valentine, Marc B.; Sublett, Jack E.; Sinclair, Anne E.; Thomas Look, A.; Tereba, Alan M.; Scheffer, Hans; Buys, Charles H. C. M.

doi: 10.1002/gcc.2870040309pmid: 1382566

A characteristic balanced reciprocal chromosomal translocation (t(2;13)(q35;q14)) has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first step in characterization of the genes involved in this translocation, we constructed somatic cell hybrids that retained either the derivative chromosome 2 or the derivative chromosome 13 without a normal chromosome 13 homologue. Ten linked DNA probes known to be located within bands 13q13‐q14 were mapped relative to the breakpoint on chromosome 13, allowing localization of the breakpoint region between two loci separated by 5.5 cM. A long‐range restriction map extending approximately 2,300 kb around these loci failed to provide evidence of rearrangement. Additionally, we confirmed that the FMS‐like tyrosine kinase gene (FLT), previously localized to 13q12 by in situ hybridization, is located proximal to the breakpoint, and we demonstrated that FLT is not a target for disruption by this tumor‐specific translocation.

Liu, Yie; Grandér, Dan; Einhorn, Stefan; Söderhäll, Stefan; Juliusson, Gunnar; Gahrton, Gösta

doi: 10.1002/gcc.2870040310pmid: 1382567

Approximately 10% of B‐cell chronic lymphocytic leukemia (B‐CLL) cases have structural chromosomal aberrations involving band 13q14. To evaluate a possible role of RB1 gene deletions in B‐CLL we investigated the malignant cells of 27 patients by molecular genetic and cytogenetic techniques. Four of the cases had chromosomal aberrations that involved 13q14 (including one case with a 13q14 deletion that was observed in a single metaphase cell), and 11 had other chromosomal abnormalities, whereas the malignant cells of 12 patients were either cytogenetically normal or failed to divide in vitro. Eight patients (30%) were found to have hemizygous deletions of the RB1 gene. These cases included all four patients with chromosomal changes at 13q14, but also three patients without chromosome abnormalities and one case with a chromosomal aberration not involving 13q. The deletions were interstitial in all cases but one, as defined by probes located centromeric and telomeric of the RB1 locus. Inactivation of RB1 may thus be a significant event in the development of some B‐CLL clones.