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Papers by Laura Schmidt

Research paper thumbnail of An evaluation of LIDAR and IFSAR-derived digital elevation models in leaf-on conditions with USGS Level 1 and Level 2 DEMs

Remote Sensing of Environment, 2003

An assessment of four different remote sensing based methods for deriving digital elevation model... more An assessment of four different remote sensing based methods for deriving digital elevation models (DEMs) was conducted in a floodprone watershed in North Carolina. New airborne LIDAR (light detecting and ranging) and IFSAR (interferometric synthetic aperture radar (SAR)) data were collected and corresponding DEMs created. These new sources were compared to two methods: Gestalt Photomapper (GPM) and contour-to-grid, used by the U.S. Geological Survey (USGS) for creating DEMs. Survey-grade points (1470) for five different land cover classes were used as reference points. One unique aspect of this study was the LIDAR and IFSAR data were collected during leafon conditions. Analyses of absolute elevation accuracy and terrain slope were conducted. The LIDAR-and contour-to-grid derived DEMs exhibited the highest overall absolute elevation accuracies. Elevation accuracy was found to vary with land cover categories. Elevation accuracy also decreased with increasing slopes-but only for the scrub/shrub land cover category. Appreciable terrain slope errors for the reference points were found with all methods. D

Research paper thumbnail of Novel mutations of the MET proto-oncogene in papillary renal carcinomas

Research paper thumbnail of Activating Mutations for the Met Tyrosine Kinase Receptor in Human Cancer

Proceedings of The National Academy of Sciences, 1997

Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary a... more Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the met cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci in vitro and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies.

Research paper thumbnail of Somatic Mutations in the Kinase Domain of the Met/Hepatocyte Growth Factor Receptor Gene in Childhood Hepatocellular Carcinomas1

The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a pol... more The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a polypeptide known as hepatocyte growth factor/scatter factor. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the tyrosine kinase domain of the MET gene (exon 15-19) in 75 primary liver cancers. Three missense mutations were detected exclusively in 10 childhood hepatocellular carcinomas (HCCs), while no mutations were detected in 16 adult HCCs, 21 cholangiocarcinomas, or 28 hepatoblastomas. The extremely short incubation period from hepatitis B virus infection to the genesis of childhood HCC as compared with the adult HCC suggests that there may be an additional mechanism that accelerates the carcinogenesis of childhood HCC. Our results indicate that mutations of the tyrosine kinase domain of the MET gene may be involved in the acceleration of the carcinogenesis in childhood HCC. . The abbreviations used are: HGF/SF, hepatocyte growth factor/scatter factor; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; SSCP, single-strand conformational polymorphism; HBs, hepatitis B surface antigen.

Research paper thumbnail of A novel germ line juxtamembrane Met mutation in human gastric cancer

Research paper thumbnail of Three tetranucleotide polymorphisms for loci: D3S1352; D3S1358; D3S1359

Human Molecular Genetics, 1993

Source/Description: Three Sau3A fragments containing an (AGAT) n repeat sequence were isolated by... more Source/Description: Three Sau3A fragments containing an (AGAT) n repeat sequence were isolated by screening a chromosome 3 cosmid library (1) using an AGAT oligonucleotide probe and subsequently subcloned into the BamHI site of the Bluescript vector. The ...

Research paper thumbnail of Hereditary and Sporadic Papillary Renal Carcinomas with c- met Mutations Share a Distinct Morphological Phenotype

American Journal of Pathology, 1999

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papil... more Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1–2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.

Research paper thumbnail of An evaluation of LIDAR and IFSAR-derived digital elevation models in leaf-on conditions with USGS Level 1 and Level 2 DEMs

Remote Sensing of Environment, 2003

An assessment of four different remote sensing based methods for deriving digital elevation model... more An assessment of four different remote sensing based methods for deriving digital elevation models (DEMs) was conducted in a floodprone watershed in North Carolina. New airborne LIDAR (light detecting and ranging) and IFSAR (interferometric synthetic aperture radar (SAR)) data were collected and corresponding DEMs created. These new sources were compared to two methods: Gestalt Photomapper (GPM) and contour-to-grid, used by the U.S. Geological Survey (USGS) for creating DEMs. Survey-grade points (1470) for five different land cover classes were used as reference points. One unique aspect of this study was the LIDAR and IFSAR data were collected during leafon conditions. Analyses of absolute elevation accuracy and terrain slope were conducted. The LIDAR-and contour-to-grid derived DEMs exhibited the highest overall absolute elevation accuracies. Elevation accuracy was found to vary with land cover categories. Elevation accuracy also decreased with increasing slopes-but only for the scrub/shrub land cover category. Appreciable terrain slope errors for the reference points were found with all methods. D

Research paper thumbnail of Novel mutations of the MET proto-oncogene in papillary renal carcinomas

Research paper thumbnail of Activating Mutations for the Met Tyrosine Kinase Receptor in Human Cancer

Proceedings of The National Academy of Sciences, 1997

Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary a... more Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the met cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci in vitro and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies.

Research paper thumbnail of Somatic Mutations in the Kinase Domain of the Met/Hepatocyte Growth Factor Receptor Gene in Childhood Hepatocellular Carcinomas1

The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a pol... more The MET protooncogene encodes a transmembrane tyrosine kinase identified as the receptor of a polypeptide known as hepatocyte growth factor/scatter factor. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the tyrosine kinase domain of the MET gene (exon 15-19) in 75 primary liver cancers. Three missense mutations were detected exclusively in 10 childhood hepatocellular carcinomas (HCCs), while no mutations were detected in 16 adult HCCs, 21 cholangiocarcinomas, or 28 hepatoblastomas. The extremely short incubation period from hepatitis B virus infection to the genesis of childhood HCC as compared with the adult HCC suggests that there may be an additional mechanism that accelerates the carcinogenesis of childhood HCC. Our results indicate that mutations of the tyrosine kinase domain of the MET gene may be involved in the acceleration of the carcinogenesis in childhood HCC. . The abbreviations used are: HGF/SF, hepatocyte growth factor/scatter factor; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; SSCP, single-strand conformational polymorphism; HBs, hepatitis B surface antigen.

Research paper thumbnail of A novel germ line juxtamembrane Met mutation in human gastric cancer

Research paper thumbnail of Three tetranucleotide polymorphisms for loci: D3S1352; D3S1358; D3S1359

Human Molecular Genetics, 1993

Source/Description: Three Sau3A fragments containing an (AGAT) n repeat sequence were isolated by... more Source/Description: Three Sau3A fragments containing an (AGAT) n repeat sequence were isolated by screening a chromosome 3 cosmid library (1) using an AGAT oligonucleotide probe and subsequently subcloned into the BamHI site of the Bluescript vector. The ...

Research paper thumbnail of Hereditary and Sporadic Papillary Renal Carcinomas with c- met Mutations Share a Distinct Morphological Phenotype

American Journal of Pathology, 1999

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papil... more Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1–2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.