Philip E. LeBoit

Bio: Philip E. LeBoit is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Nevus & Melanoma. The author has an hindex of 73, co-authored 343 publications receiving 19461 citations. Previous affiliations of Philip E. LeBoit include University of California & University of Texas at Dallas.

Distinct Sets of Genetic Alterations in Melanoma

Abstract: Background Exposure to ultraviolet light is a major causative factor in melanoma, although the relationship between risk and exposure is complex. We hypothesized that the clinical heterogeneity is explained by genetically distinct types of melanoma with different susceptibility to ultraviolet light. Methods We compared genome-wide alterations in the number of copies of DNA and mutational status of BRAF and N-RAS in 126 melanomas from four groups in which the degree of exposure to ultraviolet light differs: 30 melanomas from skin with chronic sun-induced damage and 40 melanomas from skin without such damage; 36 melanomas from palms, soles, and subungual (acral) sites; and 20 mucosal melanomas. Results We found significant differences in the frequencies of regional changes in the number of copies of DNA and mutation frequencies in BRAF among the four groups of melanomas. Samples could be correctly classified into the four groups with 70 percent accuracy on the basis of the changes in the number of copies of...

Chromosomal Gains and Losses in Primary Cutaneous Melanomas Detected by Comparative Genomic Hybridization

Abstract: The analysis of genetic changes in primary cutaneous melanoma has been limited by the need for fixation for diagnostic purposes. However, comparative genomic hybridization is able to analyze such specimens. We have applied comparative genomic hybridization to 32 primary melanomas to discover and map genomic regions with aberrant DNA copy numbers. The analysis was performed on native, nonamplified DNA extracted from manually dissected tumor sections. Loss of chromosome 9 was detected in 81% of the tumors, most commonly affecting the p arm. Additional common losses occurred on chromosomes 10 (63%), 6q (28%), and 8p (22%). Gains in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating areas harboring potential oncogenes were seen at 4q12, 5p14.3-pter, 7q33-qter, 8q12-13, 11q13.3-14.2, and 17q25. Correlations among the regions with copy number changes indicate that losses of chromosomes 9 and 10 occur early on in melanoma progression, whereas gains of chromosome 7 occur later. This sequence of events was further substantiated by an intratumoral comparison of copy number changes in areas with radial and vertical growth phase patterns. The overall pattern of regions affected by copy number changes is consistent with cytogenetic data from metastatic melanoma; however, the frequencies of involvement differ, providing further insight into the course of genetic events.

Nephrogenic fibrosing dermopathy.

Abstract: This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

Abstract: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.)

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

The cancer genome atlas pan-cancer analysis project

Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

The Cancer Genome Atlas Pan-Cancer analysis project

Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples

Abstract: The MuTect algorithm for calling somatic point mutations enables subclonal analysis of the whole-genome or whole-exome sequencing data being generated in large-scale cancer genomics projects.