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

Shan, Liang; Yang, Qifeng; Nakamura, Yasushi; Nakamura, Misa; Miyauchi, Akira; Tsujimoto, Masahiko; Nakatani, Yukio; Wakasa, Kenichi; Mori, Ichiro; Kakudo, Kennichi

doi:10.1038/modpathol.3880302

Cited by 12 publications

(4 citation statements)

References 18 publications

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“…On the other hand, in our present work, LOH of the p73 locus was not observed in all informative (GC/AT heterozygote) CRC cases, although the 1p36 locus is a site observed to have frequent loss of heterozygosity in various human cancers [36]. Pfeifer et al support our finding, since they did not show LOH of the p73 gene in 54 heterozygotic cases [22].…”

Section: Discussionsupporting

confidence: 80%

Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients

Arfaoui

Kriaa²,

Hadj

et al. 2010

Virchows Arch

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We examined the association of one linked GC/AT polymorphism at p73 with the risk of colorectal cancer. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. The p73 genotypes were determined by PCR-restriction fragment length polymorphism in 150 Tunisians patients with colorectal cancer and in 204 healthy control subjects. Immunohistochemistry was performed on normal mucosa, primary tumour and metastasis. The frequencies of the genotypes were 52% for wild-type (GC/GC), 31% for heterozygotes (GC/AT) and 17% for variants (AT/AT) in patients, and 54%, 35% and 11% in controls, respectively. There were no significant differences of the frequencies of the three genotypes between the patients and controls (p = 0.11). We did not find any relationship of the genotypes with clinicopathological features of patients. We found that patients with the AT/AT genotype had a significantly worse clinical outcome than those with the GC/AT and GC/GC genotype. There were no significant differences between tumoural immunostaining of the total p73 and p73 polymorphism (p = 0.16). However, we found a significant difference between the expression profile of DeltaNp73 isoform and frequencies of the three genotypes (p = 0.0001). No LOH was observed at p73 locus. Our results suggest that the AT/AT genotype is significantly associated with poor prognosis in colorectal cancer. All these findings suggest that p73 polymorphism analysis may provide useful prognostic information for colorectal cancer patients.

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Section: Discussionsupporting

confidence: 80%

Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients

Arfaoui

Kriaa²,

Hadj

et al. 2010

Virchows Arch

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“…A region with frequent LOH is 1p36 in different types of cancers, although the frequencies reported vary greatly (17). In addition, the more exact location has not been mapped precisely (17) and therefore we looked at the possibility that the losses could be found around the GC/AT polymorphism of the p73 gene.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism of the p73 gene in relation to colorectal cancer risk and survival

Pfeifer¹

2004

Carcinogenesis

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The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer risk are inconsistent, and the significance of loss of heterozygosity (LOH) of the gene is unclear. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. 179 patients with colorectal cancer and 260 healthy controls were genotyped for the polymorphism by PCR-restriction fragment length polymorphism (RFLP). Fifty informative cases were examined for LOH in tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n = 12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2% in controls, respectively. The frequencies of the genotypes in the patients and controls were significantly different (P = 0.02). The patients carrying the AT allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95% CI = 1.15-5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but was not significantly changed between primary tumours and metastases (P = 1.0). In conclusion, the AT/AT homozygotes may have a greater risk of developing colorectal cancer, while the patients who carried the AT allele had a better prognosis.

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“…One of these genes is p73 (1p36.33), a p53 homologue (10,11). However, extensive mutation studies showed that p73 is rarely mutated in human tumor cells (12)(13)(14). Instead, differential expression of splice variants of p73 seems associated with tumor malignancy.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of the Invasion Inhibitory Gene IIp45 by Alternative Splicing in Gliomas

Song

Fuller²,

Zheng

et al. 2005

Cancer Research

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The invasion inhibitory protein 45 (IIp45) we recently identified was underexpressed in glioblastoma multiforme, the most malignant form of glioma. The IIp45 gene is located at chromosome 1p36 where frequent deletions have been reported in various types of tumors, including gliomas, raising the possibility that IIp45 may be a classic tumor suppressor gene that can be inactivated by frequent point mutations. To test this hypothesis, we sequenced the IIp45 gene in 59 diffuse glioma samples of different grades and histologic subtypes and identified a possible point mutation or a rare polymorphism in only one sample (1.7%), suggesting that IIp45 is not a classic tumor suppressor gene such as p53. Instead, reverse transcription-PCR and subsequent sequencing results revealed a tumor-specific IIp45 spliced isoform (IIp45S) in 20 of 59 (34%) gliomas examined, particularly in glioblastoma multiformes, including native tissue samples (15 of 25; 60%) and cell lines (5 of 5; 100%). The alternative splicing event is independent of 1p36 deletion, which is not common in glioblastoma multiforme. The IIp45S transcript was not detected in any of 18 normal organs, including fetal and adult brain. We determined that the IIp45S isoform results from exclusion of IIp45 exon 7 and encodes a variant protein that carries a COOH terminus different from that of IIp45 due to a frame-shift mutation. IIp45S protein was undetectable in glioma tissues, although IIp45S mRNA was prevalent. We found that IIp45S, once translated, is rapidly degraded by an ubiquitin-proteasome mechanism. Thus, the IIp45 gene is inactivated by a tumor-specific alternative splicing that generates an aberrant and unstable IIp45 isoform in infiltrative gliomas. (Cancer Res 2005; 65(9): 3562-7)

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

Cited by 12 publications

References 18 publications

Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients

Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients

Polymorphism of the p73 gene in relation to colorectal cancer risk and survival

Inactivation of the Invasion Inhibitory Gene IIp45 by Alternative Splicing in Gliomas

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