Karen Michalski

Genomic defects in nonfamilial renal cell carcinoma: Possible specific chromosome change

Using a newly developed combined method of enzymatic technique and short-term tissue culture, 30 tumor specimens from 26 patients with nonfamilial renal cell carcinoma were subjected to cytogenetic analysis. Of the 26 patients, 19 had chromosomally abnormal tumors, four (including two oncocytomas) were normal, and three did not grow. The modal chromosome numbers ranged from 44 to 98 (including two pseudotetraploids). Banding analysis revealed 38 clonal aberrations and ten nonclonal aberrations. Abnormalities were of structure and number. The most consistent clonal abnormality was a trisomy or tetrasomy chromosome 7 occurring in tumors from 15 of the 19 patients with cytogenetically abnormal tumors. In four cases, trisomy 7 was the only visible abnormality observed, and in an additional five it was the only abnormality in two or more cells. An abnormal chromosome 3 was found in ten (38%) of the cases. Two were trisomic for #3, two were monosomic, three were hyperdiploid, and three had interstitial deletions with breakpoints clustered from p11 to p25. In only one case was a deleted #3 the only abnormality observed in a clone of cells. Loss of the sex chromosome was seen in eight (35%) of the 23 chromosomally abnormal cases including all four (100%) patients with bilateral disease. One of the patients with bilateral disease had an abnormal clone with monosomy X as the only abnormality. These data suggest that trisomy or tetrasomy 7 more often represents the specific primary abnormality than abnormalities of either chromosome 3 or the sex chromosomes. From this, a model of chromosomal progression may be constructed for nonfamilial renal cell carcinoma, which could assist in pathologic classification and prognostic and therapeutic considerations.

Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, ‐9, + DER(9)T(6:9)(p211:p24)

This report describes an adult male with a partial trisomy 6p(p211‐pter) and a partial monosomy 9p(9p24‐pter) resulting from a de novo unbalanced translocation. This patient does not show the classical features of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs not previously reported as part of the 9p monosomy or 6p trisomy syndromes.

Cytogenetics of Bilateral Renal Cell Carcinoma

We analyzed cytogenetically 6 tumors from 4 patients with bilateral renal cell carcinoma. Comparison among findings in these patients with bilateral disease and previously reported cases of unilateral tumor demonstrates that bilaterality is associated with a more frequent loss of a sex chromosome, and gain of chromosomes 7 and 3, whereas unilateral tumors often are associated with loss of chromosome 3 material. It is proposed that bilateral tumors are distinct genetically from unilateral tumors and that most bilateral tumors have a genetic propensity to either enhanced metastatic spread to other renal tissue or spontaneous degeneration.

Translocation (4;11) in acute myelogenous leukemia

A child with acute myelogenous leukemia is presented. Cytogenetic analysis of her leukemic cells revealed a (4;11)(q12;q23) translocation. The slight difference in the breakpoint on chromosome #4 from previously reported cases of t(4;11) may account for the degree of myeloid differentiation expressed. Acute leukemia associated with t(4;11) is a unique subgroup that originates in an early myeloid stem cell and carries a poor prognosis.

840 CHROMOSOME ABNORMALITIES IN OSTEOSARCOMA DEVELOPING THIRTEEN YEARS AFTER TREATMENT FOR RETINOBLASTOMA

There is a high incidence of second malignancies, especially osteosarcoma, in survivors of hereditary retinoblastoma. The retinoblastoma “gene” which has been assigned to chromosome region 13ql4 has been proposed to be a more generalized cancer gene and the link between these two diverse tumors. Non-random abnormalities, primarily deletions, have been seen in the 13ql4 region in a significant number of retinoblastoma tumor cells and is felt to be the second event. Osteosarcoma tumor cells of a right temporal bone from a 13-year-old female who had received radiation therapy (5000 R) at age 12 weeks for bilateral retinoblastoma was grown in culture and analyzed. The patient had received high-dose methotrexate 2 months before the tumor resection. Cytogenetic analysis of primary cultures show 15% with abnormalities of the #13 chromosome with 5/15 with a deletion in the 13ql4 region. Other clonal abnormalities were also noted. Simultaneous examination of peripheral lymphocytes and skin fibroblasts show 46XX normal female chromosome complement. This patient provides evidence for a common chromosomal connection between these two tumors.