The Loss of Heterozygosity in Retinoblastoma and p53 Suppressor Genes As a Prognostic Indicator for Head and Neck Cancer

Abstract

Inactivation of tumor suppressor genes, including p53 and retinoblastoma (Rb), are commonly found in all cancers, including head and neck squamous cell carcinoma. Alterations at either p53 or Rb, however, are only weakly associated with tumor aggressiveness. In many cancers loss of heterozygosity (LOH) at multiple loci is associated with decreased survival. The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA from matched sets of 63 head and neck squamous cell cancers and normal tissue for LOH at the p53 and Rb loci. At p53, 50 were informative, with LOH occurring in 19 (38%). Of the 57 that were informative at Rb, LOH occurred in 21 (37%). Of the 46 that were informative at both p53 and Rb, LOH occurred in 10 (22%) at both loci. When LOH for p53 and Rb individually was compared to stage, differentiation, and survival, there was no correlation. However, the patients with LOH at both loci had a significantly poorer survival (P = .009). This strongly supports the contention that simultaneous alterations of these two tumor suppressor genes favor tumor aggressiveness and can be used as a prognostic indicator.

The Calcium-binding Protein S100A2 Interacts with p53 and Modulates Its Transcriptional Activity

“…Changes of the subcellular localization of p53 in these tumors have been associated with inhibition of the p53 tumor suppressive function and, as a consequence, with poor prognosis (51). Overexpression of p53 is an early event in the carcinogenesis of HNSCC and correlates with increased recurrence, poor prognosis, and poor survival rate (53,54). Members of the S100 protein family have been described to enhance nuclear accumulation of p53 (32).…”

Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression

“…We further characterized the p53 status of the SCCHN tumors (patient 3 ± 12) by analysis of loss-of-hetrozygosity (LOH) (Gleich et al, 1996), and by direct sequencing of exons 5 ± 8 (Table 1, Pavelic et al, 1994). We found two tumors with deletions in one allele and a missense mutation in another allele (Table 1, patients 4 and 6), three tumors with a missence mutation (LOH not tested, patients 3, 5 and 7), one tumor with wildtype p53 sequence (LOH not tested, patient 10), and four tumors with no apparent mutation in the p53 genes (patients 8, 9, 11 and 12).…”

“…In order to detect LOH of p53 on chromosome 17, the probes p144-D6 and pYNZ22 were used to detect variable number of tandem repeat markers as described previously (Kondoleon et al, 1987;Vissing et al, 1987;Nakamura et al, 1987;Gleich et al, 1996). The LOH of p53 of the tumor samples described in this communication has been published in Gleich et al (1996).…”

“…The LOH of p53 of the tumor samples described in this communication has been published in Gleich et al (1996). Ampli®cation of p53 DNA sequences (exon 5 ± 8) using PCR was performed as previously described (Pavelic et al, 1994).…”

Variable Genetic Alterations and Survival in Head and Neck Cancer

“…3,6 This study evaluated multiple sites of potential genetic alterations that have been associated with cancer behavior to determine if there is a pattern of genetic loss associated with head and neck cancer. These genetic alterations were then com-…”