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Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RB) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic renal cell carcinoma.Three of fifteen (20 percent) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RB gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32 percent) informative cell lines had LOH centromeric to the RB gene at the D13S1 locus. No LOH (0 of 7) was seen telomeric to the RB gene at the D13S2 locus. None of the 28 cell lines examined had decreased RB mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and ...

We recently described a 3-generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Possibly family 150 is an isolated occurrence, a reflection of some as yet unknown environmental factor. Alternatively, family 150 may represent a distinct class of inherited cancer. To distinguish between these 2 possibilities we sought additional families with papillary renal cell carcinoma and we identified 9 with members affected with papillary renal cell carcinoma. There were 29 affected male and 12 affected female subjects (ratio 2.41:1), including affected members of family 150. Papillary renal cell carcinomas were often detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal cell carcinoma families. The penetrance, the proportion of obligate gene carriers that showed clinical evidence of the disease, was reduced. The median survival of affected individuals was 52 years. The results suppor...

To the Editor. Our reports in 1994 and 1995 described families with an inherited predisposition for papillary renal carcinoma. Affected family members had a predisposition for multiple papillary tumors in both kidneys. Since those reports we have learned of several European families with papillary renal carcinoma.13 In addition, we evaluated 2 new families with papillary renal carcinoma, including 1 large family from Canada.4 It is clear that papillary renal carcinoma may occur in an inherited form, and that hereditary papillary renal carcinoma represents a distinct type of inherited cancer. A feature that characterizes these papillary renal carcinoma families is the long interval between detection of papillary renal earcinoma in an individual family member and referral of the family to a major cancer genetics center. In the family pedigree shown in the figure, papillary renal carcinoma was detected in the first member in 1971 and in the second member in 1984. The family was referred to the National Cancer Institute in 1995, at which point papillary renal carcinoma had developed in 5 family members. In the Canadian family papillary renal carcinoma was diagnosed initially in 1978.4 Other family members had papillary renal carcinoma in 1980, 1980, 1984, 1985, 1987, 1990, 1990 and 1995. von Hippel-Lindau disease was diagnosed incorrectly in 1990. The family was evaluated at the National Cancer Institute in 1995, after 9 members had been diagnosed with renal cancer. Recognition that papillary renal carcinoma occurs on an inherited basis should lead to identification of additional families with this disorder. Family identification will depend on determination of family history in patients with renal tumors and on the histological type of renal carcinoma. Any family in which 2 members have papillary renal carcinoma should be referred to a cancer genetics center for further study and evaluation. The techniques to isolate the gene responsible for clear cell renal carcinomas are being used to isolate the gene(s) responsible for papillary renal carcinoma.5 The success of this effort depends on identifying additional families with papillary renal carcinoma, and studying these families in detail to detect occult renal neoplasms in asymptomatic family members.