Germ-line p53 mutation is uncommon in patients with triple primary cancers

Sekiguchi, Masayuki; Nishikawa, Ryo; Yamamoto, Hiroshi; Ochiai, Atsushi; Sugimura, Haruhiko; Shitara, Nobuyuki; Sameshima, Yuichi; Mizoguchi, Hideaki; Sügimura, Takashi; Yokota, Jun

doi:10.1016/0304-3835(93)90187-e

Cited by 25 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have assessed the frequency of deleterious variants in these genes within an MPMT cohort. Shiseki et al 35 found a pathogenic TP53 variant in one out of five patients diagnosed with three primary cancers, though that individual did conform to the Li Fraumeni syndrome (LFS) phenotype according to classical diagnostic criteria. Another analysis of TP53 in 59 cases diagnosed with a second primary cancer revealed four individuals with pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

View full text Add to dashboard Cite

Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n ¼ 62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.

show abstract

Section: Discussionmentioning

confidence: 99%

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Detailed information on these cell lines can be obtained upon request. High-molecular-weight DNA was prepared from tumors and adjacent noncancerous tissues of 45 patients with SCLC or NSCLC, and from peripheral blood samples of 42 unrelated healthy indivi-duals as described previously (Shiseki et al, 1994(Shiseki et al, , 1996Baba et al, 1995). Poly(A) RNA was prepared by the Fast Track mRNA isolation kit (Invitrogen Corp.).…”

Section: Samplesmentioning

confidence: 99%

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Kohno¹,

Shinmura

Tosaka³

et al. 1998

Oncogene

Self Cite

388

309

View full text Add to dashboard Cite

The hOGG1 gene encodes a DNA glycosylase that excises 8-hydroxyguanine (oh 8 Gua) from damaged DNA. Structural analyses of the hOGG1 gene and its transcripts were performed in normal and lung cancer cells. Due to a genetic polymorphism at codon 326, hOGG1-Ser 326 and hOGG1-Cys 326 proteins were produced in human cells. Activity in the repair of oh 8 Gua was greater in hOGG1-Ser 326 protein than in hOGG1-Cys 326 protein in the complementation assay of an E. coli mutant defective in the repair of oh 8 Gua. Two isoforms of hOGG1 transcripts produced by alternative splicing encoded distinct hOGG1 proteins: one with and the other without a putative nuclear localization signal. Loss of heterozygosity at the hOGG1 locus was frequently (15/ 23, 62.2%) detected in lung cancer cells, and a cell line NCI-H526 had a mutation leading to the formation of the transcripts encoding a truncated hOGG1 protein. However, the oh 8 Gua levels in nuclear DNA were similar among lung cancer cells and leukocytes irrespective of the type of hOGG1 proteins expressed. These results suggest that the oh 8 Gua levels are maintained at a steady level, even though multiple hOGG1 proteins are produced due to genetic polymorphisms, mutations and alternative splicing of the hOGG1 gene.

show abstract

“…Finally, studies of patients selected on the basis of multiple primary tumours Shiseki et al, 1993;Russo et al, 1994) have shown that they have germline TP53 mutations at a frequency of between 7% and 20%.…”

Section: Germline Tp53 Mutations In Patients With Tumours Typical Of Lfsmentioning

confidence: 99%

Li-Fraumeni syndrome – a molecular and clinical review

Varley

Evans²,

Birch³

1997

Br J Cancer

318

180

View full text Add to dashboard Cite

Germ-line p53 mutation is uncommon in patients with triple primary cancers

Cited by 25 publications

References 16 publications

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

Li-Fraumeni syndrome – a molecular and clinical review

Contact Info

Product

Resources

About