Deletions of the Short Arm of Chromosome 3 in Solid Tumors and the Search for Suppressor Genes

Kok, Klaas; Naylor, Susan L.; Buys, Charles H.C.M.

doi:10.1016/s0065-230x(08)60096-2

Cited by 299 publications

(244 citation statements)

References 276 publications

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“…12 There are several candidate TSGs on the p-arm, including Von Hippel-Lindau (VHL) at 3p25-26, Xeroderma Pigmentosum C (XPC) at 3p25, hMLH1 at 3p21.3, and fragile histidine triad (FHIT) at 3p14.2; however, to date, no TSG has been identified of the q-arm. 12,13 Monosomy 3 in uveal melanomas is predominantly found in tumours that result in metastatic disease, suggesting that its occurrence results in the loss of TSGs, which, either alone or in combination with other genetic abnormalities, are prerequisites for metastatic disease. 10,11,20 As the entire chromosome is lost, it seems likely that several TSGs residing on both arms are the targets, and thus in a single genetic event a reduction to homozygosity for all relevant genes would be achieved.…”

Section: Discussionmentioning

confidence: 99%

“…12 Deletions of chromosome 3 are frequently observed in many tumour types, although such abnormalities tend to affect only chromosome 3p, with 3q deletions being a relatively rare event. 13 Uveal melanomas, however, are highly unusual in that the entire chromosome is subject to loss, and it has been hypothesised that these observations reflect the involvement of one or more TSGs on each chromosomal arm. 10,11,14 A minority of uveal melanomas do however demonstrate translocations and partial deletions of chromosome 3, occasionally as the sole abnormality.…”

Section: Introductionmentioning

confidence: 99%

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Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

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Ganesh

Parpia

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

Cross

Ganesh

Parpia

et al. 2005

Eye

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“…Involvement of the short arm of chromosome 3 in various different cancers has been known for some time (Kok et al, 1997). Frequent allelic loss and homozygous deletions of 3p are one of the earliest molecular changes in tumours of the lung, kidney, head and neck, breast, cervix and gastrointestinal tract (Hung et al, 1995;Kok et al, 1997;Wistuba et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Frequent allelic loss and homozygous deletions of 3p are one of the earliest molecular changes in tumours of the lung, kidney, head and neck, breast, cervix and gastrointestinal tract (Hung et al, 1995;Kok et al, 1997;Wistuba et al, 2000). High-resolution studies of tumours refined the areas of allelic losses in 3p into several distinct regions representing likely locations of tumour-suppressor genes (TSGs).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the 3p21.3 tumour-suppressor gene cluster

2007

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“…9 Candidate genes in the smallest overlapping regions 4q12-q23 10 and 4q31-q35, on the other hands, remains undescribed. 11,12 As regions of aberrant genomic loci can harbor more than one tumor-related genes, such as RASSF1A, MLH1, TGFBR2 and BLU on chromosome 3p21, [13][14][15][16] the existence of more than one tumor-suppressor gene within common deleted sites of hepatocellular carcinoma cannot be ruled out.…”

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confidence: 99%

Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma

et al. 2006

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Molecular characterizations of hepatocellular carcinoma have indicated frequent allelic losses on chromosomes 4q, 8p, 16q and 17p, where the minimal deleted regions have been further defined on 4q12-q23, 4q31-q35, 8p21-p22, 16q12.1-q23.1 and 17p13. Despite these regions are now well-recognized in early liver carcinogenesis, few underlying candidate genes have been identified. In an effort to define affected genes within common deleted loci of hepatocellular carcinoma, we conducted transcriptional mapping by highresolution cDNA microarray analysis. In 20 hepatocellular carcinoma cell lines and 20 primary tumors studied, consistent downregulations of novel transcripts were highlighted throughout the entire genome and within sites of frequent losses. The array-derived candidates including fibrinogen gamma peptide (FGG, at 4q31.3), vitamin D binding protein (at 4q13.3), fibrinogen-like 1 (FGL1, at 8p22), metallothionein 1G (MT1G, at 16q12.2) and alpha-2-plasmin inhibitor (SERPINF2, at 17p13) were confirmed by quantitative reverse transcriptionpolymerase chain reaction, which also indicated a more profound downregulation of FGL1, MT1G and SERPINF2 relative to reported tumor-suppressor genes, such as DLC1 (8p22), E-cadherin (16q22.1) and TP53 (17p13.1). In primary hepatocellular carcinoma examined, a significant repression of MT1G by more than 100-fold was indicated in 63% of tumors compared to the adjacent nonmalignant liver (P ¼ 0.0001). Significant downregulations of FGG, FGL1 and SERPINF2 were also suggested in 30, 23 and 33% of cases, respectively, compared to their nonmalignant counterparts (Po0.016). In summary, transcriptional mapping by microarray indicated a number of previously undescribed downregulated genes in hepatocellular carcinoma, and highlighted potential candidates within common deleted regions. Keywords: hepatocellular carcinoma; deletion hotspots; cDNA array; transcriptional mapping Hepatocellular carcinoma currently ranks the fifth most common malignancy worldwide. 1,2 It carries a high cancer morbidity and mortality because by the time of clinical presentation, more than 80% of patients are at the advance inoperable stage. 2,3 The low efficacy of current screening regime by serum alpha-fetoprotein measurements and transabdominal ultrasound imaging has rendered most patients not being diagnosed in time for curative surgery.Thus, underpinning the genetic events associated with hepatocellular carcinoma is expected to improve our understanding on liver carcinogenesis and also potentially provide biomarkers that are of diagnosis and prognostic values.Molecular studies using loss of heterozygosity analysis and comparative genomic hybridization have revealed recurrent chromosomal changes in hepatocellular carcinoma including losses on 1p, 4q, 6q, 8p, 11q, 13q, 16q and 17p. [4][5][6] As diminutions on 4q, 8p, 16q and 17p have been described in the nontumorous cirrhotic nodules and early preneoplastic liver dysplasia, these changes have been further implicated in the early carcinogenetic events of hepat...

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Deletions of the Short Arm of Chromosome 3 in Solid Tumors and the Search for Suppressor Genes

Cited by 299 publications

References 276 publications

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

Evaluation of the 3p21.3 tumour-suppressor gene cluster

Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma

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