Table of Contents
1
UI - 11835679
AU - Boyle JM; Spreadborough AR; Greaves MJ; Birch JM; Varley JM; Scott D
TI -
Delayed chromosome changes in gamma-irradiated normal and Li-Fraumeni
fibroblasts.
SO - Radiat Res 2002 Feb;157(2):158-65
AD - CRC Cancer Genetics Group, Paterson Institute for Cancer Research,
Christie Hospital NHS Trust, Manchester M20 9BX, United Kingdom.
Knockout mice with only one Trp53 allele (+/- genotype) are highly
susceptible to radiation-induced cancers, possibly through numerical
chromosome changes. Patients with the Li-Fraumeni syndrome, having
heterozygous TP53 germline mutations (+/mut genotype), are also
susceptible to spontaneous and radiogenic cancers. We have investigated
the susceptibility of six Li-Fraumeni syndrome +/mut and six normal
fibroblast strains to induced numerical and unstable structural
aberrations at six population doublings after exposure to 3 or 6 Gy
gamma rays. Four of the irradiated Li-Fraumeni syndrome strains showed
small increases in both aberration types, similar to those seen in the
normal strains. In two irradiated Li-Fraumeni syndrome strains, there
were high levels of induced structural changes, and one of these showed
a modest increase in hyperploidy. We suggest that enhanced sensitivity
to delayed radiation-induced chromosome changes in Li-Fraumeni syndrome
cells requires other genetic alterations in addition to TP53
heterozygosity, apparently in contrast to the situation in Trp53
heterozygous null mice. If such additional alterations occur in vivo in
Li-Fraumeni syndrome patients, they may predispose them to radiogenic
cancers, mainly through enhanced structural rather than numerical
chromosome changes. Our findings raise questions about the validity of
quantitative extrapolation of cytogenetic data from Trp53-defective mice
to radiogenic cancer risk in humans.
2
UI - 11826360
AU - Wyatt-Ashmead J; Kleinschmidt-DeMasters B; Mierau GW; Malkin D; Orsini
TI -
E; McGavran L; Foreman NK
Choroid plexus carcinomas and rhabdoid tumors: phenotypic and genotypic
overlap.
SO - Pediatr Dev Pathol 2001 Nov-Dec;4(6):545-9
AD - Pathology Department, The Children's Hospital, 1056 East 19th Avenue
B120, Denver, CO 80218, USA.
Five of six poorly differentiated choroid plexus carcinomas identified
at our institution contained cells displaying a rhabdoid phenotype.
Immunoperoxidase stains showed focal positivity for cytokeratin,
epithelial membrane antigen, glial fibrillary acidic protein, S100, and
vimentin. The MIB-1 proliferative index ranged from 7.0% to 27.1%. All
six tumors were p53 positive. Only the one child with Li-Fraumeni
syndrome had a p53 germline mutation. Electron microscopy verified
choroid plexus differentiation and the co-existence of rhabdoid cells.
Of the five studied, four had deletions of chromosome 22 [three with
monosomy 22 and one with del(22)(q12)]. Thus, there was a phenotypic and
genotypic overlap between choroid plexus carcinomas and rhabdoid tumors.
3
UI - 11822026
AU - Shete S; Amos CI; Hwang SJ; Strong LC
TI -
Individual-specific liability groups in genetic linkage, with
applications to kindreds with Li-Fraumeni syndrome.
SO - Am J Hum Genet 2002 Mar;70(3):813-7
AD - Department of Epidemiology, The University of Texas M. D. Anderson
Cancer Center, Houston, TX 77030, USA. sshete@mdanderson.org
In this report, we present a simple and powerful way to incorporate
individual-specific liability classes into linkage analysis. The
proposed method is applicable to both quantitative and qualitative
traits. In linkage studies, we may have information about different
covariates. Incorporation of these covariates along with the estimates
of residual familial effects, age-at-onset effects, and susceptibility
in the definition of liability classes can increase the power to detect
genetic linkage. In this study, we show how one can form
individual-specific liability classes and use these classes in standard
linkage-analysis programs, such as the widely used LINKAGE package, to
perform more powerful genetic linkage analysis. Our simulation study
shows that this approach yields higher LOD scores and more-accurate
estimates of the recombination fraction in the families showing linkage.
The proposed method is also applied to kindreds collected, at the M. D.
Anderson Cancer Center, through probands with childhood soft-tissue
sarcoma. Confirmed germ-line mutations in the p53 tumor-suppressor gene
have been identified in these families. Application of our method to
these families yielded significantly higher LOD scores and more-accurate
recombination fractions than did analysis that did not account for
individual-specific covariate information.
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