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Clinical and Genetic Studies of Renal Cell Carcinomas in a Family with a Constitutional Chromosome 3; 8 Translocation: Genetics of Familial Renal Carcinoma

Frederick P. Li, MD; Hans-Joachim H. Decker, MD; Bert Zbar, MD; Vincent P. Stanton, MD; Gyula Kovacs, MD; Bernd R. Seizinger, MD, PhD; Hiroyuki Aburatani, MD, PhD; Avery A. Sandberg, MD; Solomon Berg, MD; Shigeto Hosoe, MD; and Robert S. Brown, MD
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From the National Cancer Institute, Bethesda, Maryland; Dana-Farber Cancer Institute, Harvard School of Public Health, Beth Israel Hospital, and Massachusetts General Hospital, Boston, Massachusetts; Massachusetts Institute of Technology, Cambridge, Massachusetts; Southwest Biomedical Research Institute, Scottsdale, Arizona. Requests for Reprints: Frederick P. Li, MD, Dana-Farber Cancer Institute, 44 Binney Street, Mayer 3A.27, Boston, MA 02115. Acknowledgments: The authors thank Margaret Dreyfus for technical and clerical assistance. The work of Vincent Stanton and Hiroyuki Aburatani was done in the laboratory of David Housman, PhD. Grant Support: In part by grants RO1 CA49455, HG00299, and HL41484 from the National Cancer Institute and by a Faculty Research Award from the American Cancer Society.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(2):106-111. doi:10.7326/0003-4819-118-2-199301150-00005
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Objective: To describe the clinical course and genetic studies of renal carcinoma in members of a family with the constitutional chromosome translocation, t(3; 8) (p14; q24).

Design: A follow-up study that updates our 1979 report of renal carcinoma in 10 of these relatives.

Setting: A cancer center and university hospital.

Patients: Members of the family, including five carriers of the 3; 8 translocation who were in remission of renal cancer.

Measurements: Clinical follow-up of the family and genetic analyses of the renal cancer specimens of three patients.

Results: Renal carcinoma recurred in all five patients in the family at 1 to 16 years of follow-up. Three patients have died of renal cancer, and two are in a second remission. The renal cancers from three family members consistently reveal loss of the entire derivative chromosome 8, which bears the chromosome 3p segment spanning band p14 to the telomere. In contrast, no genetic change was detected in the derivative chromosome 3 or in normal chromosomes 3 and 8.

Conclusions: This family illustrates the importance of clinical follow-up of patients with a hereditary cancer that can develop at multiple foci and recur over time. The inherited 3; 8 translocation and loss of the translocated distal chromosome 3p in tumor specimens of family members may help localize the gene or genes involved in the pathogenesis of both familial and sporadic renal carcinoma.


Grahic Jump Location
Figure 1.
Abridged pedigree of the family with a constitutional 3; 8 translocation.

Four generations (I to IV) with the translocation (T) are shown. Squares indicate men, circles indicate women, and diamonds indicate persons of either gender. Clear-cell carcinoma of the kidney had developed in 10 relatives, whose symbol is crosshatched if cancer had been the cause of death before 1979 and blackened if cancer recurred between 1979 and 1990. Persons who have died have a diagonal line across the symbol. During the follow-up period, all five patients (Patients II-4, III-1, 2, 13, and 14) who had been in remission of renal carcinoma have developed new foci of the neoplasm. Three of them have died of the cancer. In addition, two of these patients (Patients III-13 and 14) have developed thyroid carcinoma (C).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Representative karyotype of renal carcinoma cells of patient III-1.

The tumor cells show clonal loss of the entire derivative chromosome 8. The karyotype is as follows: 43,XX,-3,+der (3)t(3;8)t(p14.2;q24), −8,−13,−14,−16,+der(16)t(13;?;16) (pterq>24::?::>13q1-g13qter).

Grahic Jump Location
Grahic Jump Location
Figure 3.
Renal cancer cells of Patient III-1 show allelic loss at THRB restriction site on the derivative chromosome 8.[1, 2]

Her normal (N) cells are heterozygous . The direct extract of her tumor (TUa) shows a diminished signal for allele 1, presumably due to the presence of admixed nontumor cells. Allele 1 is undetectable after the tumor specimen (TUb) was cultured for several days to remove nontumor components.

Grahic Jump Location




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