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Alisa M. Goldstein

Bio: Alisa M. Goldstein is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Population & Cancer. The author has an hindex of 72, co-authored 297 publications receiving 22773 citations. Previous affiliations of Alisa M. Goldstein include United States Department of Health and Human Services.


Papers
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Journal ArticleDOI
14 Jun 1996-Cell
TL;DR: It is proposed that a reduction in expression of the patched gene can lead to the developmental abnormalities observed in the syndrome and that complete loss of patched function contributes to transformation of certain cell types.

1,970 citations

Journal ArticleDOI
TL;DR: Nine melanoma-specific mutations were detected in 9p21-linked, but not in 1p36- linked, families, thereby confirming previous reports of genetic heterogeneity and will confirm those causally related to the development of familial melanoma.
Abstract: The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splice donor site and six missense) in 13/18 familial melanoma kindreds. Six of these mutations were identified in 33/36 melanoma cases in nine families, whereas two were detected in normal controls and are not disease-related. The melanoma-specific mutations were detected in 9p21-linked, but not in 1p36-linked, families, thereby confirming previous reports of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial melanoma.

1,225 citations

Journal ArticleDOI
TL;DR: The frequency of the clinical and radiological anomalies in Nevoid basal cell carcinoma syndrome in a large population of US patients is delineated and guidelines for diagnosis and management are discussed.
Abstract: Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a meanmore » age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include {open_quotes}coarse face{close_quotes} in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. 48 refs., 3 figs., 5 tabs.« less

856 citations

Journal ArticleDOI
TL;DR: Age-adjusted chordoma incidence rate was age-dependent, more common in males than females, and rare among patients aged <40 years and blacks, and racial disparities in incidence for the two developmental tumors, chordoma and Ewing's sarcoma were revealed.
Abstract: Background: Chordoma, a rare tumor arising from notochordal remnants, has been described to date only by single-institution case series or small population-based surveys.

807 citations

Journal ArticleDOI
TL;DR: It is reported that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele.
Abstract: The sonic hedgehog (SHH) signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Pathway activation is triggered by binding of hedgehog proteins to the multipass Patched-1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets. Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal-cell carcinomas, medulloblastomas and other cancers (a pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele. Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism.

799 citations


Cited by
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Journal Article
Fumio Tajima1
30 Oct 1989-Genomics
TL;DR: It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.

11,521 citations

Journal ArticleDOI
06 Jun 2013-Cell
TL;DR: Nine tentative hallmarks that represent common denominators of aging in different organisms are enumerated, with special emphasis on mammalian aging, to identify pharmaceutical targets to improve human health during aging, with minimal side effects.

9,980 citations

Journal ArticleDOI
TL;DR: The use of MSP is demonstrated to identify promoter region hypermethylation changes associated with transcriptional inactivation in four important tumor suppressor genes (p16, p15, E-cadherin and von Hippel-Lindau) in human cancer.
Abstract: Precise mapping of DNA methylation patterns in CpG islands has become essential for understanding diverse biological processes such as the regulation of imprinted genes, X chromosome inactivation, and tumor suppressor gene silencing in human cancer. We describe a new method, MSP (methylation-specific PCR), which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes. This assay entails initial modification of DNA by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequent amplification with primers specific for methylated versus unmethylated DNA. MSP requires only small quantities of DNA, is sensitive to 0.1% methylated alleles of a given CpG island locus, and can be performed on DNA extracted from paraffin-embedded samples. MSP eliminates the false positive results inherent to previous PCR-based approaches which relied on differential restriction enzyme cleavage to distinguish methylated from unmethylated DNA. In this study, we demonstrate the use of MSP to identify promoter region hypermethylation changes associated with transcriptional inactivation in four important tumor suppressor genes (p16, p15, E-cadherin, and von Hippel-Lindau) in human cancer.

5,847 citations

Journal ArticleDOI
TL;DR: Specific standards designed to maintain rigor while also promoting communication are proposed for the interpretation of linkage results in genetic studies under way for many complex traits.
Abstract: Genetic studies are under way for many complex traits, spurred by the recent feasibility of whole genome scans. Clear guidelines for the interpretation of linkage results are needed to avoid a flood of false positive claims. At the same time, an overly cautious approach runs the risk of causing true hints of linkage to be missed. We address this problem by proposing specific standards designed to maintain rigor while also promoting communication.

5,317 citations

Journal ArticleDOI
18 Oct 1996-Cell
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.

4,959 citations