| Identity |
| Note | Renal cell carcinomas (RCC) represent 85% of all primary renal tumors. In general, RCCs are sporadic tumors but cases of familial RCC have also been reported. If detected early and without metastases, the disease can be cured surgically with conservation of renal function. Both familial and sporadic cases have in common the presence of abnormalities involving chromosome 3, suggesting a primary role for this chromosome in RCC causation, particularly the clear cell type. An early gene rearrangement due to translocation may be a primary event. Loss of 3p and somatic mutation(s) in a tumor-surpressor-gene(s) on 3p (e.g.VHL) may be recurring events related to tumor progression |
| Inheritance |
The inherited form of renal cancer is characterized by : - the tumor is found at an early age compared to sporadic tumors (see below) - the tumors are found frequently bilateral - multiple occurrence. Other (well known) classes of inherited renal cell carcinomas are: Also chromosome abnormalities may be related to inherited renal cancer. |
| Clinics |
| Note | No phenotypic sign. |
| Neoplastic risk | Multiple and/or bilateral nonpapillary renal cell carcinomas, with median age 45 yrs at diagnosis (range 18-79 yrs, most cases being between 35 and 55 yrs old). |
| Treatment | If the tumor is detected at an early stage the tumor can be surgical removed, without the lost of the renal function. |
| Prognosis | Depends on the stage of the tumor at the time of detection. |
| Cytogenetics |
| Note | Clear-cell renal cell carcinomas are associated with chromosome 3 translocations and deletions of 3p. |
| Genes involved and Proteins |
| Gene Name | FHIT |
| Location | 3p14.2 |
| Note | FHIT is a breakpoint spanning gene on chromosome 3 in a constitutional familial case of a t(3;8)(p14;q24) translocation. |
| DNA/RNA | |
| Description | 10 exons |
| Protein | |
| Description | 147 amino acids |
| Gene Name | TRC8 |
| Location | 8q24 |
| Note | TRC8 is a breakpoint spanning gene on chromosome 8 in a constitutional familial case of a t(3;8)(p14;q24) translocation. |
| Gene Name | DIRC2 |
| Location | 3q21 |
| Note | Dirc2 is a breakpointspanning gene on chromosome 3 in a constitutional familial case of a t(2;3)(q35;q21) translocation. |
| DNA/RNA | |
| Description | The gene spans 73 kb, 9 exons. |
| Protein | |
| Description | 478 amino acids |
| Expression | Expression in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain and heart. |
| Localisation | Proximal tubular cells of the kidney. |
| Function | May be a transporter. |
| Gene Name | DIRC3 |
| Location | 2q35 |
| Note | Dirc3 is a breakpointspanning gene on chromosome 2 in a constitutional familial case of a t(2;3)(q35;q21) translocation. |
| DNA/RNA | |
| Description | The gene spans 3071 bp and contains 12 exons. |
| Gene Name | DIRC1 |
| Location | 2q33 |
| Note | Dirc1 is a breakpointspanning gene on chromosome 2 in a constitutional familial case of a t(2;3)(q33;q22) translocation. |
| DNA/RNA | |
| Description | DIRC1 gene contains 2 exons and spans approximately 57 kb of genomic DNA |
| To be noted |
| External links |
| Orphanet | Renal cell carcinoma, familial |
| Bibliography |
| A new inducible fragile site on chromosome 3(p14.2) in human lymphocytes. |
| Wegner RD |
| Human genetics. 1983 ; 63 (3) : 297-298. |
| PMID 6852828 |
| Involvement of band 3p14 in t(3;8) hereditary renal carcinoma. |
| Wang N, Perkins KL |
| Cancer genetics and cytogenetics. 1984 ; 11 (4) : 479-481. |
| PMID 6704944 |
| An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation. |
| Bodmer D, Eleveld MJ, Ligtenberg MJ, Weterman MA, Janssen BA, Smeets DF, de Wit PE, van den Berg A, van den Berg E, Koolen MI, Geurts van Kessel A |
| American journal of human genetics. 1998 ; 62 (6) : 1475-1483. |
| PMID 9585616 |
| The DIRC1 gene at chromosome 2q33 spans a familial RCC-associated t(2;3)(q33;q21) chromosome translocation. |
| Druck T, Podolski J, Byrski T, Wyrwicz L, Zajaczek S, Kata G, Borowka A, Lubinski J, Huebner K |
| Journal of human genetics. 2001 ; 46 (10) : 583-589. |
| PMID 11587072 |
| Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation. |
| Podolski J, Byrski T, Zajaczek S, Druck T, Zimonjic DB, Popescu NC, Kata G, Borowka A, Gronwald J, Lubinski J, Huebner K |
| Journal of human genetics. 2001 ; 46 (12) : 685-693. |
| PMID 11776380 |
| Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). |
| Bodmer D, Eleveld M, Kater-Baats E, Janssen I, Janssen B, Weterman M, Schoenmakers E, Nickerson M, Linehan M, Zbar B, van Kessel AG |
| Human molecular genetics. 2002 ; 11 (6) : 641-649. |
| PMID 11912179 |
| The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway. |
| Gemmill RM, Bemis LT, Lee JP, Sozen MA, Baron A, Zeng C, Erickson PF, Hooper JE, Drabkin HA |
| Oncogene. 2002 ; 21 (22) : 3507-3516. |
| PMID 12032852 |
| Disruption of a novel gene, DIRC3, and expression of DIRC3-HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21). |
| Bodmer D, Schepens M, Eleveld MJ, Schoenmakers EF, Geurts van Kessel A |
| Genes, chromosomes & cancer. 2003 ; 38 (2) : 107-116. |
| PMID 12939738 |
| Molecular study of a new family with hereditary renal cell carcinoma and a translocation t(3;8)(p13;q24.1). |
| Melˆ©ndez B, Rodrˆ‚guez-Perales S, Martˆ‚nez-Delgado B, Otero I, Robledo M, Martˆ‚nez-Ramˆ‚rez A, Ruiz-Llorente S, Urioste M, Cigudosa JC, Benˆ‚tez J |
| Human genetics. 2003 ; 112 (2) : 178-185. |
| PMID 12522559 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 10-2003 | Anita Bonné, Danielle Bodmer, Marc Eleveld, Eric Schoenmakers, Ad Geurts van Kessel |
| Department of Human Genetics (417), P.O. Box 9101, 6500 HB Nijmegen, The Netherlands |
| Citation |
| This paper should be referenced as such : |
| Bonné A, Bodmer D, Eleveld M, Schoenmakers EFPMG, Geurts van Kessel A . Familial clear cell renal cancer. Atlas Genet Cytogenet Oncol Haematol. October 2003 . URL : http://AtlasGeneticsOncology.org/Kprones/FamClearCellRenalID10081.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Feb 10 18:14:20 CET 2010 |
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