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Biomedical subjects

F P Li

Publications and source records attributed to F P Li.

At least 37 records · Page 2Linked to original sources
PubMed1998

Constitutional WT1 mutations in Wilms' tumor patients.

PURPOSE: Patients with Wilms' tumors (WT) who carry constitutional mutations in the WT1 gene have been described in case reports and small case series. We sought to determine the frequency of constitutional WT1 mutations in a larger cohort, and to identify clinical manifestations associated with the risk for carrying a WT1 mutation. METHODS: We collected clinical data and blood samples from 201 patients with a history of WT. Southern blot analysis, single-strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing were performed on DNA isolated from peripheral-blood lymphocytes from each patient. Odds ratios (ORs) for the carriage of a germline mutation of the WT1 gene were calculated for patients who had specific clinical risk factors compared with those who did not. RESULTS: Of 201 patients with WT in the cohort, eight patients were carriers of mutations in the WT1 gene. Six of the eight mutations were protein-truncating nonsense mutations. None of 56 patients with isolated unilateral WT was a carrier. The OR of carrying a WT1 mutation was elevated for patients with genitourinary anomalies (OR19.3; P < .002). Seven of 28 boys with WT with cryptorchidism carried WT1 mutations. No increased risk was observed for patients with nephrogenic rests, bilateral tumors, history of secondary cancers, or family history of WT. CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias. Patients with WT and no genitourinary anomalies are at low risk for carrying a WT1 mutation. Constitutional WT1 mutations that encode truncated WT1 proteins may predispose to the development of cryptorchidism, hypospadias, and WTs.

Adolescent↗
PubMed1998

Carcinoembryonic antigen in breast nipple aspirate fluid.

New diagnostic tools are needed to complement mammography and physical examinations for early detection of breast cancer, particularly among younger women. We evaluated the tumor biomarker, carcinoembryonic antigen (CEA), in 215 nipple aspirate fluid (NAF) samples collected from one or both breasts of 147 women, ages 27-87 years. Most subjects were recruited at the time of mammography examination. The 215 nipple fluid CEAs range from undetectable levels to 8400 ng/ml (median, 1100 ng/ml). Normal serum CEA levels are less than 6 ng/ml. There are no significant differences between the CEAs in fluid from normal breasts (112 samples) and breasts with various histories of tumors (total, 103 samples). Analyses for determinants of CEAs in fluids from normal breasts show higher levels among current smokers (P = 0.03) and marginal elevations among nulliparous women (P = 0.07). CEAs in these samples are not correlated with age, menopausal status, current hormone use, prior breastfeeding, or family history of breast cancer. Follow-up studies of these women and comparisons of CEAs in fluids from normal and cancer-containing breasts will help clarify whether this biomarker is useful for risk assessment or early cancer detection.

Adult↗
PubMed1997

Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk.

CONTEXT: There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. OBJECTIVE: To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. DESIGN: Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas. SETTING/PARTICIPANTS: A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984. RESULTS: Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05). CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.

Adolescent↗
PubMed1997

Evidence for genetic heterogeneity in familial Wilms' tumor.

Wilms' tumor (WT), a childhood kidney cancer, occurs both sporadically and, less frequently, in a familial context. Genetic linkage studies of several large WT families have excluded the one cloned WT gene, WT1, as the locus responsible for familial predisposition. These data demonstrate the existence of a familial predisposition gene distinct from WT1 and, more broadly, imply that the genetic etiology of WT is heterogenous. However, it has been unknown whether the predisposition observed in large WT families is also heterogenous or perhaps is due to mutations at a single locus. Recently, examination of a large French-Canadian WT family has demonstrated genetic linkage to 17q12-q21. We report here the results from a genetic linkage study of six WT pedigrees. Analyses of genotype data from eight loci within the 17q12-q21 region in these families resulted in cumulative lod scores of <-4.0 through the region, thereby excluding linkage. The ability to rule out the 17q region as the site of a predisposition gene in several of these pedigrees individually demonstrates the existence of more than one gene that predisposes to WT in large pedigrees and again emphasizes that the etiology of WT is genetically heterogenous.

Adult↗
PubMed1997

Molecular epidemiology study of a suspected community cluster of childhood cancers.

We investigated the report of a community cluster of cancers in 33 children, which included two siblings known to have dominantly inherited Li-Fraumeni syndrome and a germline p53 mutation. After defining criteria for inclusion in the cluster, the 12 eligible childhood cancer probands diagnosed between 1980 and 1989 were not excessive (expected, ten cases). The corresponding childhood cancer mortality rates for the community fluctuated between 1950 and 1989 and were not increased overall. However, three additional probands had family histories of childhood cancer that suggested a forme fruste of Li-Fraumeni syndrome. The epidemiological data suggested a geographic cluster of this rare hereditary disorder, but absence of germline p53 mutation in the three other multicase families indicates genetic heterogeneity. Laboratory studies can assist analyses of suspected clusters, although investigations of geographic clusters of hereditary cancers raise complex issues of confidentiality and protection of affected individuals, their families, and the community.

Adolescent↗
PubMed1996

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2.

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.

Acute Disease↗
PubMed1996

Germline WT1 mutations in Wilms' tumor patients: preliminary results.

We conducted a comparative study of the prevalence of germline WT1 mutations in patients with Wilms' tumor. Patients in Group 1 have familial Wilms' tumor, bilateral disease, associated urogenital anomalies, and/or second cancers. Those in Group 2 are unilateral, sporadic Wilms' patients without other associated conditions. Patients with aniridia or Denys-Drash syndrome are known to have WT1 alterations, and are excluded from this study. Preliminary results on 96 subjects show that the overall germline WT1 mutation frequency is low (< 5%). The work to date establishes the feasibility of identifying patients with germline WT1 mutations and, in the future, offering genetic predisposition testing to at-risk relatives. However, genetic predisposition testing of children for WT1 mutations raises many ethical, legal, and psychosocial issues; research is needed to evaluate risks and benefits.

Base Sequence↗
PubMed1996

Mutational scanning of large genes by extensive PCR multiplexing and two-dimensional electrophoresis: application to the RB1 gene.

With the rapid increase in the number of identified human disease genes, the development of accurate and cost-efficient mutation tests has become opportune. Here we present a combination of extensive PCR multiplexing and two-dimensional (2-D) DNA electrophoresis to screen for mutations in 26 exons of the retinoblastoma (RB1) tumor suppressor gene. In 2-D electrophoresis, fragments are separated according to size and base pair sequence in non-denaturing and denaturing gradient gels, respectively. All target fragments, designed to have optimal melting characteristics, were prepared in a two-step PCR (a 6-plex long-PCR pre-amplification and a subsequent 25-plex short-PCR) followed by heteroduplexing. The mixture of PCR amplicons was then subjected to 2-D electrophoresis under a single set of experimental conditions. With this design, 35 previously identified mutations in 18 different exons were detected in 33 bilateral retinoblastoma patients. These results suggest that 2-D electrophoresis in this format provides a generally applicable, practical and fast way to diagnose with high accuracy large genes for a broad spectrum of possible disease-causing mutations.

DNA Mutational Analysis↗