Atlas of Genetics and Cytogenetics in Oncology and Haematology
RASSF1 Ras association (RalGDS/AF-6) domain family member 1
| Identity |
| Other names | 123F2 |
| RDA32 | |
| REH3P21 | |
| HGNC (Hugo) | RASSF1 |
| Location | 3p21.3 |
| Location_base_pair | Starts at 50342221 and ends at 50353371 bp from pter ( according to hg18-Mar_2006) [Mapping] |
| Local_order | telomeric to BLU and centromeric to FUS1 |
| Note | RASSF1 is also known as NORE2A. More correctly, NORE must be considered a paralog of RASSF1, a human ortholog of mouse NoreA. genomic clones: cosmid LUCA 12 and LUCA 13 |
| DNA/RNA |
 | |
| Grey: exon 1a, green: exon 1b; blue: exon 2ab; yellow : exon 2g; brown: exons 3,4, 5, 6. Arrows: transcription start sites. CpG: location of CpG islands. RASSF1A and RASSF1B start with exon 1a and 1b respectively. The second exon (2ab) is common to both forms. Exon 2g is the first exon of RASSF1C and is present in this transcript only. | |
| Description | the genomic size of the gene is about 7.6 kb. |
| Transcription | At least three alternative transcripts were identified (A, B and C) that originate from alternative splicing and promoter usage. Exons 3 to 6 are common to all forms. Transcript A has two 5' exons (designated 1a and 2ab), this cDNA is 1,873 bp (ORF: 340 amino acids). RASSF1B first exon is designated 1b and is different from RASSF1A. Exon two is 2ab as in transcript A. cDNA size: 1,664 bp. Transcript RASSF1C first exon is designated 2g, cDNA size 1700 bp (ORF 270 amino acids). |
| Pseudogene | no known pseudogenes. |
| Protein |
 | |
| Schematic representation of RASSF1 protein variants, as deduced from the transcripts. | |
| Description | The carboxy terminus of RASSF1A shows about 55% identity to the mouse protein Nore1 and the rat protein Maxp1, both are Ras effector proteins (Nore1 was shown to interact in vivo with Ras upon receptor activation in a GTP-dependent manner). RASSF1A N terminus has high homology with a domain known as protein kinase C conserved region 1 domain (a cysteine-rich diacylglycerol/phorbol ester binding domain). RASSF1B most likely is constituted only of the Ras association domain. |
| Expression | RASSF1A and RASSF1C are expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, small intestine, colon, peripheral blood leukocytes. RASSF1B is expressed predominantly in cells of hematopoietic origin. |
| Localisation | not determined. |
| Function | RASSF1 binds Ras in a GTP-dependent manner and may serve as the effector that mediates Ras apoptotic effects. Alternatively, it may sequester RAS proteins thereby regulating the availability of these proteins for signaling. |
| Mutations |
| Note | single nucleotide polymorphism (SNP) in exon 1a: AAG (Lys21)/CAG (Gln21). |
| Somatic | Mutations were rarely found. In non small cell lung cancer four were found: GAC (Asp129) to GAG (Glu129); ATT (Ile135) to ACT (Thr135); CGG (Arg257) to CAG (Gln257); GCC (Ala336) to ACC (Thr336). |
| Implicated in |
| Entity | clear cell renal carcinoma and papillary renal carcinoma; lung cancer; ovarian cancer; prostate cancer, gastric adenocarcinoma; bladder carcinoma; nasopharingeal carcinoma; breast cancer. |
| Note | The mechanism of inactivation of this tumor suppressor consists in promoter hypermethylation. The gene promoter was found hypermetylated in 90 % of primary kidney tumors and 40 % of lung tumors. Hypermethylation and loss of transcription were causally related. Hypermethylation occurs in variable percentage in other tumors and indicate a role for this gene in malignant progression (62 % of bladder carcinoma; 49 % of breast tumors; 40 % of ovarian tumors; 12 % of colon cancer). |
| External links |
| Bibliography |
| Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. |
| Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP |
| Nature genetics. 2000 ; 25 (3) : 315-319. |
| PMID 10888881 |
| The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. |
| Lerman MI, Minna JD |
| Cancer research. 2000 ; 60 (21) : 6116-6133. |
| PMID 11085536 |
| Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. |
| Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ |
| The Journal of biological chemistry. 2000 ; 275 (46) : 35669-35672. |
| PMID 10998413 |
| Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. |
| Agathanggelou A, Honorio S, Macartney DP, Martinez A, Dallol A, Rader J, Fullwood P, Chauhan A, Walker R, Shaw JA, Hosoe S, Lerman MI, Minna JD, Maher ER, Latif F |
| Oncogene. 2001 ; 20 (12) : 1509-1518. |
| PMID 11313894 |
| Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. |
| Burbee DG, Forgacs E, Zchbauer-Mşller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M, Minna JD |
| Journal of the National Cancer Institute. 2001 ; 93 (9) : 691-699. |
| PMID 11333291 |
| Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma. |
| Byun DS, Lee MG, Chae KS, Ryu BG, Chi SG |
| Cancer research. 2001 ; 61 (19) : 7034-7038. |
| PMID 11585730 |
| The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinomas. |
| Dammann R, Takahashi T, Pfeifer GP |
| Oncogene. 2001 ; 20 (27) : 3563-3567. |
| PMID 11429703 |
| Hypermethylation of the cpG island of Ras association domain family 1A (RASSF1A), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers. |
| Dammann R, Yang G, Pfeifer GP |
| Cancer research. 2001 ; 61 (7) : 3105-3109. |
| PMID 11306494 |
| The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. |
| Dreijerink K, Braga E, Kuzmin I, Geil L, Duh FM, Angeloni D, Zbar B, Lerman MI, Stanbridge EJ, Minna JD, Protopopov A, Li J, Kashuba V, Klein G, Zabarovsky ER |
| Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (13) : 7504-7509. |
| PMID 11390984 |
| Frequent epigenetic inactivation of RASSF1A in human bladder carcinoma. |
| Lee MG, Kim HY, Byun DS, Lee SJ, Lee CH, Kim JI, Chang SG, Chi SG |
| Cancer research. 2001 ; 61 (18) : 6688-6692. |
| PMID 11559536 |
| High frequency of promoter hypermethylation of RASSF1A in nasopharyngeal carcinoma. |
| Lo KW, Kwong J, Hui AB, Chan SY, To KF, Chan AS, Chow LS, Teo PM, Johnson PJ, Huang DP |
| Cancer research. 2001 ; 61 (10) : 3877-3881. |
| PMID 11358799 |
| Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear cell and papillary renal cell carcinoma. |
| Morrissey C, Martinez A, Zatyka M, Agathanggelou A, Honorio S, Astuti D, Morgan NV, Moch H, Richards FM, Kishida T, Yao M, Schraml P, Latif F, Maher ER |
| Cancer research. 2001 ; 61 (19) : 7277-7281. |
| PMID 11585766 |
| Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. |
| Yoon JH, Dammann R, Pfeifer GP |
| International journal of cancer. Journal international du cancer. 2001 ; 94 (2) : 212-217. |
| PMID 11668500 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 12-2001 | Debora Angeloni, Michael I. Lerman |
| Citation |
| This paper should be referenced as such : |
| Angeloni D, Lerman MI . RASSF1 Ras association (RalGDS/AF-6) domain family member 1. Atlas Genet Cytogenet Oncol Haematol. December 2001 . URL : http://AtlasGeneticsOncology.org/Genes/RASSF1ID377.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Feb 27 10:52:19 CET 2010 |
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