p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent

Ichimiya, Shingo; Nimura, Yuji; Kageyama, Hajime; Takada, Naoyuki; Sunahara, Masao; Shishikura, Tomotane; Nakamura, Yohko; Sato, Shigeru; Seki, Naohiko; Ohira, Miki; Kaneko, Yasuhiko; McKeon, Frank; Caput, Daniel; Nakagawara, Akira

doi:10.1038/sj.onc.1202390

Cited by 108 publications

(86 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Allelic loss of p73 gene was analyzed using the CT repeat-length polymorphism within Intron 9 of the p73 gene (10). PCR amplification was carried out for 35 cycles under the following conditions: 45 seconds at 95°C, 30 seconds at 55°C, and 30 seconds at 72°C using the following primers: sense, 5'-CCTCTTCCTCCCCTACCAAC-3' and antisense, 5'-TAGGCGACAGAGCAAGACG-3'.…”

Section: Allelic Loss Analysis Of P73 Genementioning

confidence: 99%

“…To localize the gene responsible for parathyroid tumorigenesis, loss of heterozygosity (LOH) has been analyzed in various loci, and different frequencies of LOH have been identified (2,3). For example, LOH at 1q21-32 (the locus for the hyperparathyroidism and jaw tumor syndrome), 3q (the locus of calcium-sensing receptor gene), 6q, 11q13 (the locus of MEN 1 gene), and 15q has been detected in 18,10,30,38, and 35% of adenomas respectively. Among the various loci, 1p is the one of the most frequent to show LOH in parathyroid adenomas.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

et al. 2001

View full text Add to dashboard Cite

Although 1p is one of the most common loci showing loss of heterozygosity (LOH) in primary parathyroid adenoma, fine mapping has not been previously examined. In this study, we analyzed LOH in 32 primary parathyroid adenomas using five microsatellite markers at 1p36 (proximal-D1S507-D1S450-D1S2893-D1S468-D1S243-distal). All cases were heterozygous for at least one marker. The frequency of LOH varied from 41.2% (D1S468) to 7.1% (D1S507) among the different markers. LOH was detected consistently in a group of nine adenomas (28.1%, 9/32). A single region (7 cM) showing a consistent LOH at 1p36.3 was obtained that was flanked distally by D1S468 and proximally by D1S2893. Because the p73 gene is localized within this region and acts as a tumor suppressor gene, we examined the possible involvement of p73 in the development of parathyroid tumor. Allelic loss of p73 was identified in four adenomas (25%, 4/16 informative cases) that were all from the group of the nine adenomas with LOH, but somatic mutation was not detected in the remaining allele. At the StyI polymorphism of Exon 2, four of the six adenomas with LOH at 1p36 were heterozygous and expressed the GC allele. Of the six heterozygous adenomas without LOH, 4 showed biallelic and 2 monoallelic expressions (GC allele). All adenomas mainly expressed the p73␣ isoform. p73 protein was observed in five of the six adenomas with LOH and in two of the six adenomas without LOH. There were no differences in p73 protein levels between the samples with and without LOH. In conclusion, a candidate gene for parathyroid tumorigenesis is present within a 7-cM region at 1p36.3, however p73 is unlikely to be the target of the LOH at 1p36.3. KEY WORDS: 1p36, Hyperparathyroidism, Loss of heterozygosity, Parathyroid neoplasia, p73. Mod Pathol 2001;14(4):273-278Parathyroid adenoma is one of the most common endocrine tumors, characterized by excessive secretion of parathyroid hormone (PTH) and enlargement of mostly one parathyroid gland. The molecular mechanism of parathyroid tumorigenesis is still poorly understood (1). MEN 1 gene abnormality has been found in only about 20% of the sporadic parathyroid adenomas. Cyclin D1/PTH gene rearrangement seems to be involved only in a small subset of these tumors, and p53 gene mutations also appear to be rare. To localize the gene responsible for parathyroid tumorigenesis, loss of heterozygosity (LOH) has been analyzed in various loci, and different frequencies of LOH have been identified (2, 3

show abstract

Section: Allelic Loss Analysis Of P73 Genementioning

confidence: 99%

mentioning

confidence: 99%

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Monoallelic expression or the reactivation of a silenced p73 allele were also observed and this raised the possibility that this gene might be subjected to imprinting (Mai et al, 1998a,b;Nomoto et al, 1998;Chi et al, 1999;Corn et al, 1999;Kawano et al, 1999;Ichimiya et al, 1999;Peters et al, 1999;Romani et al, 1999a;Zaika et al, 1999;Scaru et al, 2000). Genomic imprinting could be of particular importance in neuroblastoma.…”

mentioning

confidence: 99%

Methylation-independent silencing of the p73 gene in neuroblastoma

2000

View full text Add to dashboard Cite

“…14,15,[18][19][20]51 Importantly, even in neuroblastomas, recent data on p73 deletion, mutation, and expression argue that p73 is unlikely to be a tumor suppressor gene inactivated during neuroblastoma development. 52 Second, we present data showing that p53 deletions also occur only in a minority of MM patients. As observed with p73 deletions, the presence of p53 deletions was associated with stage III disease.…”

Section: Discussionmentioning

confidence: 78%

True

1999

Leukemia

View full text Add to dashboard Cite

Recently, p73, a protein with structural and functional similarities to p53, an extensively studied tumor suppressor gene, has been cloned. After being mapped to the chromosomal region 1p35-1p36, it has been postulated to act as a tumor suppressor gene, too, as this region is altered in several human malignancies. Deletions of the short arm of chromosome 1 have frequently been described in multiple myeloma (MM) whereas structural abnormalities of the 17p13 region including p53 are rare events in this disease. Since it has been proposed that especially neoplasias lacking p53 alterations might show a loss of heterozygosity at 1p35-1p36, we studied the frequency of p53 and p73 deletions in bone marrow mononuclear cells of 68 patients with MM, two patients with monoclonal gammopathy of undetermined significance and four patients with plasma cell leukemia. Dual-color fluorescence in situ hybridization (FISH) for p53 and p73 was performed using commercially available DNA probes for 17p13.3 and the microsatellite marker D1Z2, respectively. Centromeric DNA probes served to distinguish gene deletions from whole chromosome losses. In contrast to recently published FISH results, we only detected heterozygous p53 deletions in eight out of the 74 patients, three of them showing a monosomy 17. Heterozygous deletions of the D1Z2 region at 1p36 were found in six cases with one patient having a monosomy 1. Neither homozygous deletions of either chromosomal region nor nullisomies 1 or 17 could be detected. These results argue against a major role of p73 deletions in MM. As MM patients with 1p structural abnormalities have a significantly poorer survival rate than those with normal karyotypes, the role of other putative tumor suppressor genes located at the chromosomal region 1p36 in the pathogenesis of MM has to be determined.

show abstract

p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent

Cited by 108 publications

References 23 publications

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

Frequent Loss of Heterozygosity at 1p36.3 and p73 Abnormality in Parathyroid Adenomas

Methylation-independent silencing of the p73 gene in neuroblastoma

True

Contact Info

Product

Resources

About