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Regional Loss of Chromosome 6 in Two Urological Malignancies

Division of Urology, Brigham and Women's Hospital, Boston, Massachusetts 02215 [D. B. R., J. P. R.]; Division of Hematology-Oncology, Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215 [G. J. B.]; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115 [J. G. S.]; Division of Urology, Indiana University Medical Center, Indianapolis, Indiana 46223 [J. P. D.]; and Divisions of Urology and Cellular Genetics, Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215 [W.C. D.]

Immunogenetic evidence suggests a genetic association between the major histocompatibility complex and the two genitourinary neoplasms, testicular teratocarcinoma and renal cell carcinoma. In order to develop a possible explanation for these findings, we designed a series of experiments to investigate the existence of a tumor suppressor gene in the region of HLA by looking for loss of germ line heterozygosity in these neoplasms at loci within and centramene to HLA on chromosome 6. Restriction enzyme-digested DNA, from 15 human teratocarcinoma tumors, and corresponding normal somatic DNA, from peripheral blood mononuclear cells, were hybridized to one of three chromosome 6 probes determined to be polymorphic in this region. Probe 4c11 (6p11-cen) revealed loss of germ line DNA in three of 14 tumors. In contrast, probes pC22A (6p21.3) and p308 (6cen), which hybridize to chromosome 6p sequences, telomeric and centramene to those sequences recognized by 4c11, did not demonstrate loss or sequence alteration in a total of 14 analyzable tumors. A total of 33 renal cell carcinoma specimens was also analyzed with the informative 4c11 probe with loss demonstrated in six of 33 tumors. In contrast, 23 different samples representing 15 other tumor types were examined with 4c11. Loss of chromosome 6p DNA was demonstrated in only two samples. These data support the hypothesis that there is nonrandom loss of DNA centromeric to HLA on chromosome 6 in both testicular teratocarcinoma and renal cell carcinoma.

¹ To whom requests for reprints should be addressed.

Received 2/21/89. Revised 4/25/89. Accepted 6/ 8/89.

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