Human breast cancer: frequent p53 allele loss and protein overexpression

Singh, Surjit; Simon, Manuel; Meybohm, I.; Jantke, I.; Jonat, W.; Maaß, H.; Goedde, H. W.

doi:10.1007/bf00202481

Cited by 37 publications

(24 citation statements)

References 24 publications

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“…British Journal of Cancer (1998) 77(5) YNZ22 allelic imbalance reported in this study (52%) lies within the range (37-65%) previously published by other groups (Chen et al, 1991;Singh et al, 1993;Thorlacius et al, 1993;Comelis et al, 1994;Harada et al, 1994;Ito et al, 1995;Stack et al, 1995). The proportion of cancers with p53 mutation (20%), p53 allele loss (41%), p53 mRNA expression (54%) and overexpression (28%) or p53 protein expression (32%) are similar to the reported series (Cattoretti et al, 1988;Davidoff, 1991;Iwaya, 1991;Kovach et al, 1991;Osborne et al, 1991;Runnebaum et al, 1991;Varley et al, 1991;Vojtesek et al, 1992;Andersen et al, 1993;Barnes, 1993;Friedrichs, 1993;Martinazzi, 1993;Thorlacius et al, 1993;Tsuda et al, 1993;Marks et al, 1994;Bergh et al, 1995;Borressen et al, 1995;Stenmark-Askmalm et al, 1995).…”

Section: Discussionsupporting

confidence: 84%

“…Although YNZ22 allelic imbalance may occur in the same tumour as p53 mutation (Chen et al, 1991;Cornelis et al, 1994; seven out of ten patients in this study) it is clearly no longer tenable to suggest that YNZ22 allelic imbalance occurs only in the presence of p53 mutation (Singh et al, 1993) and the two may in fact be quite dissociated (Chen et al, 1996).…”

Section: Discussionmentioning

confidence: 56%

“…Up to two-thirds of tumours may show allelic imbalance at the YNZ22 locus at 17pl3.3 (Mackay et al, 1988;Devilee et al, 1989;Thompson et al, 1990;Chen et al, 1991;Singh et al, 1993;Thorlacius et al, 1993;Cornelis et al, 1994;Harada et al, 1994;Stack et al, 1995) and this finding has been associated with markers of tumour aggression Chen et al, 1991;Merlo et al, 1992;Harada et al, 1994;Ito et al, 1995).…”

mentioning

confidence: 99%

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Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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Summary Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41 %) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (1 7p1 3.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

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Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Thompson

Crichton²,

Elton³

et al. 1998

Br J Cancer

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“…CGH has been used extensively to detect amplifications and large homozygous deletions, and LOH has been used to detect regions of allelic homogeneity indicative of hemizygous deletions or copy-neutral LOH. LOH is typically assessed through the analysis of polymorphic genetic markers, traditionally either VNTRs or RFLPs (Singh et al 1993;Dockhorn-Dworniczak et al 1994), and more recently single nucleotide polymorphisms (SNPs) (Slater et al 2005;Zheng et al 2005). The importance of LOH is underscored by its extensive history in the discovery of many classical tumor-suppressor genes (TSGs) including RB1, WT1, and TP53, involved in the formation of retinoblastoma, Wilm's tumor, and Li-Fraumeni syndrome, respectively (Gray and Collins 2000;Hanahan and Weinberg 2000;Albertson and Pinkel 2003;.…”

mentioning

confidence: 99%

High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping

Peiffer¹,

Le²,

Steemers³

et al. 2006

Genome Res.

475

498

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Array-CGH is a powerful tool for the detection of chromosomal aberrations. The introduction of high-density SNP genotyping technology to genomic profiling, termed SNP-CGH, represents a further advance, since simultaneous measurement of both signal intensity variations and changes in allelic composition makes it possible to detect both copy number changes and copy-neutral loss-of-heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP loci, to detect chromosomal aberrations in samples bearing constitutional aberrations as well tumor samples at sub-100 kb effective resolution. Detected aberrations include homozygous deletions, hemizygous deletions, copy-neutral LOH, duplications, and amplifications. The statistical ability to detect common aberrations was modeled by analysis of an X chromosome titration model system, and sensitivity was modeled by titration of gDNA from a tumor cell with that of its paired normal cell line. Analysis was facilitated by using a genome browser that plots log ratios of normalized intensities and allelic ratios along the chromosomes. We developed two modes of SNP-CGH analysis, a single sample and a paired sample mode. The single sample mode computes log intensity ratios and allelic ratios by referencing to canonical genotype clusters generated from ∼120 reference samples, whereas the paired sample mode uses a paired normal reference sample from the same individual. Finally, the two analysis modes are compared and contrasted for their utility in analyzing different types of input gDNA: low input amounts, fragmented gDNA, and Phi29 whole-genome pre-amplified DNA.

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“…1994) and at various rates in virtually every other human malignancy (Levine et al, 1991;Hollstein et al, 1991). The genetic lesions most often revealed are missense point mutations in evolutionarily conserved regions of the p53 gene (Mazars et al, 1992), usually accompanied by loss of the corresponding wild-type allele (Radford et al, 1993;Singh et al, 1993). Because the expression of mutant, stabilised p53 protein is highly correlated with p53 gene mutation (Davidoff et al, 1991;Hurlimann et al, 1994;Tsuda and Hirohashi, 1994), demonstration of intracellular p53 protein accumulation, usually by immunohistochemical means, is an established alternative to the more laborious molecular techniques.…”

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confidence: 99%

Immunofluorometric analysis of p53 protein and prostate-specific antigen in breast tumours and their association with other prognostic indicators

Levesque

Gm²,

Yu³

et al. 1995

Br J Cancer

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Suman Mutation and overexpression of p53 occurs in 20-40% of breast cancers and has been shown to be an independent prognostic indicator. Recently we have demonstrated prostate-specific antigen (PSA) expression in breast tumours to be suggestive of favourable prognosis, but quantitative relationships between PSA and p53. and between these and other prognostic factors in breast cancer, have not been investigated. Time-resolved immunofluorometric procedures were used to quantify both p53 protein and PSA in 200 breast tumour extracts, which were also assayed for oestrogen (ER) and progesterone receptors (PGR), epidermal growvth factor receptors (EGFR). cathepsin D and HER-2 neu, and characterised for S-phase fraction and DNA ploidy. Weak Spearman correlations were found between p53 and ER (r = -0.18, P = 0.010), PGR (r = -0.15. P = 0.0385) and S-phase fraction (r = 0.17. P = 0.016). while PSA was correlated only with PGR (r = 0.16. P = 0.025). Wilcoxon rank sum analysis revealed that levels of ER (P = 0.0001), PGR (P = 0.0001).S-phase fraction (P = 0.0001) and EGFR (P= 0.0014) differed significantly between the two groups categorised as p53 negative or p53 positive. Tumours classifed as PSA negative or PSA positive were found to differ with respect to PGR (P =0.0091) and S-phase fraction (P = 0.011) in a similar analysis. Contingency tables indicated significant negative associations betweeh the status of p53 and that of ER (P = 0.003) and PGR (P =0.001) and between PSA and S-phase fraction (P = 0.012). and positive associations between p53 and EGFR (P = 0.017), HER-2 neu (P = 0.008). S-phase fraction (P = 0.001) and aneuploidy (P= 0.007), and between PSA and both ER (P = 0.061) and PGR (P = 0.010). No significant associations were found between p53 and PSA. Our results demonstrate that the presence of p53 in breast tumours relates to several other variables which are suspected to predict aggressive tumour phenotypes and that the presence of PSA relates to variables associated with good prognosis.

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Human breast cancer: frequent p53 allele loss and protein overexpression

Cited by 37 publications

References 24 publications

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up

High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping

Immunofluorometric analysis of p53 protein and prostate-specific antigen in breast tumours and their association with other prognostic indicators

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