Familial clear cell renal cancer

Identity

Atlas_Id	10081
Genes implicated in	DIRC1  DIRC2  DIRC3  FHIT  RNF139
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: the Von Hippel-Lindau syndrome, and the Lynch syndrome II. 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
Alias	AP3A HYDROLASE FRAGILE SITE 3p14.2, INCLUDED FRA3B, INCLUDED
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	RNF139
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

Bibliography

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

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

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

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

Molecular study of a new family with hereditary renal cell carcinoma and a translocation t(3;8)(p13;q24.1).

Meléndez B, Rodríguez-Perales S, Martínez-Delgado B, Otero I, Robledo M, Martínez-Ramí A, Ruiz-Llorente S, Urioste M, Cigudosa JC, Benítez J

Human genetics. 2003 ; 112 (2) : 178-185.

PMID 12522559

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

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

A new inducible fragile site on chromosome 3(p14.2) in human lymphocytes.

Wegner RD

Human genetics. 1983 ; 63 (3) : 297-298.

PMID 6852828

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. 2004;8(1):57-58.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/FamClearCellRenalID10081.html

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