Loss of heterozygosity on chromosome 5q in ovarian cancer is frequently accompanied by TP53 mutation and identifies a tumour suppressor gene locus at 5q13.1-21

Abstract

Summary Forty-nine ovarian tumours were examined for loss of heterozygosity (LOH) on chromosome 5 using eight microsatellite markers spanning both arms, including one at the APC locus. LOH on Sq was a frequent event, detectable in 23 of 49 (47%) tumours, whereas 5p LOH was detected in only 1 of 22 tumours (5%). Six tumours showed partial LOH on 5q, enabling the candidate region to be localised to a 22 cM region proximal to APC, flanked by D5S424 and D5S644. An association was found between 5q LOH and TP53 mutation, with 18 of 23 (78%) tumours with LOH on Sq also harbouring a TP53 mutation. LOH on Sq was observed in 6 of 18 (33%) stage I tumours, suggesting that it may be an early event in the molecular pathogenesis of certain ovarian carcinomas.

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis

“…There was lack of similar strong correlation between mutations and chromosome 7 alterations, as none with isolated -7/7q-had TP53 mutation, which is a novel finding. The close association between mutations of TP53 and specifically -5/5q-in de novo MDS is intriguing and needs further functional analysis, although such a correlation exists in tMDS (Christiansen et al, 2001) and solid cancers (Tavassoli et al, 1996). Such a finding raises the possibility of an integral link between 5q and TP53 mutations, building on a related suggestion that haploinsufficiency of RPS14 in 5q-patients is driving TP53 expression levels (Dutt et al, 2011).…”

Frequent loss of heterozygosity at the DNA mismatch-repair loci hMLH1 and hMSH3 in sporadic breast cancer

“…Delimited by D5S418 and D5S647, this SRO is 43.5 cM away from APC and MCC (Figure 3). Allelic losses at 5q13.1Ðq21 in 33% of ovarian cancers (Tavassoli et al, 1996) as well as in 42% of NSCLC (Benachenhou et al, 1998b) also occurred outside the APC-containing region. Thus, genes other than APC/MCC have to be considered as targets of 5q11Ðq13 deletions.…”

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

“…The exons screened varied across studies (exons 5-8 in 14 studies; 26,36,42,48,58,59,93,103,116,119,127,131,132,134 exons 5-9 in 9 studies; 78 135 ). Among those studies in which exons 5-8 or exons 5-9 were evaluated, the p53 mutation prevalence estimates were similar: 42% (95% CI, 38 -46%) and 43% (95% CI, 47-59%), respectively.…”

“…17 122,131,132 In the majority of the studies, the tumors initially were screened for mutations using a combination of polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) 17 93 temporal temperature gradient electrophoresis, 135 constant denaturant gel electrophoresis, 58 and denaturing gradient gel electrophoresis 58 ), chemical mismatch cleavage, 128 and heteroduplex analysis. 89 DNA sequencing was used exclusively in 4 studies, 26 …”