Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas.

Onco gen: Human oncogene locations and chromosome aberrations

Clustering of aberrations to specific chromosomes in human neoplasms. IV. A survey of 1,871 cases.

This survey of chromosomal aberrations in human neoplasms comprises 1,871 cases distributed on 15 groups of malignant disease, viz. 4 groups of myeloproliferative disorders with 1,328 cases, 5 groups of lymphoproliferative disorders with 369 cases and 6 groups of solid tumors with 174 cases. The material is presented in 17 tables, in which the variation of each chromosome is listed separately for each geographic region. In the discussion part a number of special problems are looked into. The difference in variation between the individual chromosomes was highly signifcant statistically. Within each tumor, all chromosomes which exceeded the average variation with more than 1 standard deviation were considered selectively involved. In all neoplasms taken together, the chromosomes selectively involved clustered to 15 of the 24 human chromosome types. Other topics taken up for discussion were the following: possible differences in chromosome variation between geographic regions; the specificity of certain marker chromosomes; the hypothesis of 2 essentially different kinds of chromosome aberration in cancer. The phenomena of genic amplification and recurrent translocation often found in cancer require the assumption of unorthodox cytogenetic mechanisms. One main conclusion of the paper is that the aberrations of the selectively involved chromosomes influence cancer development because of the genes they carry.

Clustering of aberrations to specific chromosomes in human neoplasms

Molecular analysis of mbcl-2: Structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma

The chromosomes of uncultured cells of the near-diploid mouse plasmacytoma MOPC-31C were studied. The modal number of chromosomes was 44. The tumor lacked two marker chromosomes, reciprocal translocation [rcp t(12; 15)], that in previous studies were found to be common to 3 other uncultured myelomas and 1 cultured mouse myeloma. Through the formation of two markers, rcp t(6; 15), unique to this tumor, however, the tumor shared with other tumors and their specific markers a common breakpoint in chromosome "15 at band D3/E. This breakpoint has been found in all mouse plasmacytomas examined with banding thus far and is considered of possible importance in the development of this tumor.

A Specific Chromosome Breakpoint Associated With Mouse Plasmacytomas

Two common chromosome markers in the 2 plasmacytomas previously examined by Giemsa banding were consistently present in the mouse plasmacytoma X-5563, a transplantable hypertetraploid tumor of spontaneous origin in C3H mice. The 2 markers were found in both induced and spontaneous tumors and in either BALB/c or C3H mice. The derived cell line had 17 fewer chromosomes than the X-5563 tumor and was oncogenic, and its modal karyotype was identical to that of the tumor transmitted by the inoculation of the cell line. The homogeneity of a slight karyotypic modification in a second tumor suggested a possible clonal origin of that tumor. The high frequency of centric fusions between homologues and the structure of certain markers suggests that homologue association may precede marker formation. We proposed a second mechanism of marker formation, selective regional elongation, to account for the larger number of markers with proximal or distal elongations without evidence of translocation and for the observed alterations in length and banding pattern of markers after growth in vitro. Comparison of MOPC-21, MOPC-315, and X-5563 tumors showed preferential involvement of certain chromosomes in marker formation, an inferred association of the 2 common markers with an early stage in the origin of the 3 plasmacytomas, and consistent loss of an X chromosome. Loss of oncogenicity in cell lines was associated with a number of karyotypic changes, but did not require the loss of the characteristic markers or additional copies of a specific normal chromosome.

Karyotype, marker formation, and oncogenicity in mouse plasmacytomas.

Spontaneous loss of oncogenicity has been found to occur in cultured mouse myeloma cells. A cell line SLU-J27, established from mouse myeloma MOPC-315, was shown to be quite similar in karyotype and tumorigenicity to the tumor of origin. Both contained two markers previously shown to be consistently present in another myeloma, MOPC-21, and in five derived cell lines. These were: a No. 12 chromosome with an extra terminal band and a partially deleted No. 15 chromosome. The SLU-J27 cell line contained two populations that differed in having one or two X chromosomes. When this cell line was inoculated into mice, the resultant tumors were all derivatives of the “2X” population. With time in culture the 2X population gained two new markers and the oncogenicity of the cell line decreased. 5-Bromodeoxyuridineresistant lines derived from SLU-J27 had only the 2X modal karyotype. All centric fusions were between homologs, with one possible exception, suggesting homolog association.

Alterations of Karyotype and Oncogenicity in Mouse Myeloma MOPC-315 and 5-Bromodeoxyuridine-resistant Cell Lines

A reproducible association between loss of tumorigenicity and specific karyotypic changes was described in cell culture lines SLU-5 and DMS-402 established from mouse plasmacytoma MOPC-21 carried in BALB/c mice. The defect in chromosome no. 15, which has been specifically associated with mouse myelomas, was neither corrected nor eliminated in the karyotypic evolution that occurred simultaneously and progressively with the grandual loss of oncogenicity.

June S. Shepard

Papers

A Specific Chromosome Breakpoint Associated With Mouse Plasmacytomas

Karyotype, marker formation, and oncogenicity in mouse plasmacytomas.

Alterations of Karyotype and Oncogenicity in Mouse Myeloma MOPC-315 and 5-Bromodeoxyuridine-resistant Cell Lines

Karyotypic Evolution Associated With Loss of Tumorigenicity