Showing papers by "Albert de la Chapelle published in 2016"
Mayo Clinic1, Baylor University Medical Center2, Baylor College of Medicine3, University of Melbourne4, Ohio State University5, University of California, Irvine6, Memorial Sloan Kettering Cancer Center7, Royal Melbourne Hospital8, Creighton University9, Harvard University10, University of Texas MD Anderson Cancer Center11, Auckland City Hospital12, University of Toronto13, Fred Hutchinson Cancer Research Center14, University of Hawaii15, University of California, San Francisco16
TL;DR: The authors recommend against reducing cancer surveillance guidelines in families found having monoallelic PMS2 mutations in spite of the reduced penetrance, as it is currently unknown what causes the early onset of CRC in some families with MonoallelicPMS2 germline mutations.
57 citations
TL;DR: Comprehensive expression screening identified 2 novel lncRNAs associated with risk factors of adverse prognosis in PTC patients and may be novel players in P TC carcinogenesis.
Abstract: Context: Long noncoding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. Objective: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. Design: We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters. The 2 most significantly dysregulated lncRNAs were studied in an Ohio PTC cohort (n = 109) and in PTC data (n = 497) from The Cancer Genome Atlas. Setting: A combination of laboratory-based studies and computational analysis using clinical data and samples and a publically available database. Main Outcome Measures: Correlation between expression values and clinical parameters. Results: We identified 218 lncRNAs showing differential expression in PTC (fold change ≥ 2.0, P < .01). Significant correlation was observed between the expression of 2 lncRNAs (XL...
45 citations
TL;DR: Most patients with colorectal or endometrial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations in PIK3CA; mutations in pik3CA are detected at substantially higher frequencies in these double somatic tumors than in other microsatellite-instability subgroups.
35 citations
TL;DR: The results show that germline variants not only predispose to PTC but also might impact its clinical course, however, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variant in the clinical stratification of PTC patients.
Abstract: Background: Papillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients. Methods: In order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants (PTCSC3, MBIP, NKX2-1, FOXE1, DIRC3, PTCSC2, and NRG1) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score....
33 citations
TL;DR: Examination of the extent of HABP2 variant involvement in papillary thyroid carcinoma shows lack of any involvement, and it is suggested that the putative role of variant HabP2 in PTC should be carefully scrutinized.
Abstract: The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80–90% of all thyroid malignancies. Only 3–10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.
31 citations
TL;DR: CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis, and overall survival was longer in patients with LS; this difference was minimal after adjusting for age and stage at diagnosis.
27 citations
TL;DR: The aim of the present study was to type coding and noncoding thyroid markers in different culture systems in an attempt to determine the optimal conditions for in vitro experimentation.
Abstract: Background: Cell models are key instruments for in vitro studies of the thyroid. Permanent thyroid cell lines that are widely used in laboratory research typically originate from tumors. For many purposes, it is desirable to compare tumor cells with cells originating from normal tissue. However, such cultures grow slowly, have a highly limited life-span, and are known to lose their thyroid characteristics. The aim of the present study was to type coding and noncoding thyroid markers in different culture systems in an attempt to determine the optimal conditions for in vitro experimentation. Methods: Human primary thyroid cells were isolated from histologically non-tumorous tissues. Two alternative media (6H and h7H) were used. The morphology and behavior of the ensuing monolayer (two-dimensional) cultures was monitored by microscopy. The expression of key thyroid-related genes (n = 9) was monitored by reverse transcription polymerase chain reaction on days 8, 21, and 43 after initiation. As a pilot study, ...
16 citations
TL;DR: Both Caster Semenya and Dutee Chand had pivotal, although inadvertent, involvement in the evolution of the currently suspended hyperandrogenism (testosterone) policies of the International Olympic Committee (IOC) and the International Association of Athletic Federations (IAAF).
Abstract: At least 2 women athletes subjected to intense media scrutiny in the past several years—Caster Semenya and Dutee Chand—are likely to attract additional attention in the forthcoming 2016 Summer Olympic Games in Brazil. Both women had pivotal, although inadvertent, involvement in the evolution of the currently suspended hyperandrogenism (testosterone) policies of the International Olympic Committee (IOC) and of the International Association of Athletic Federations (IAAF). Competitors had raised concerns regarding their “masculine” appearance and eligibility, and these concerns were further amplified by an intrusive media and social media. Semenya emerged suddenly at the IAAF’s 2009 World Games in Berlin, where she easily won the 800meter event—even though her time was far from the world record. Her appearance prompted complaints from her competitors and provoked her suspension pending thorough medical evaluation. Upon return to competition several months later, Semenya’s appearance was unchanged and she remained highly competitive but no longer excelled. Ultimately her case contributed to development of the so-called hyperandrogenism policy, which established a testosterone eligibility threshold of 10 nmol/L (288 ng/dL) for female athletes, unless the athlete is demonstrated to be insensitive to tes-
15 citations
TL;DR: The characterization of miR-3662 has identified a new actor in the prominent hematopoietic quantitative trait locus in chromosome 6q23.3, and directly targets NF-κB-mediated transcription.
Abstract: Chromosomal aberrations and multiple genome-wide association studies (GWAS) have established a major hematopoietic quantitative trait locus in chromosome 6q23.3. The locus comprises an active enhancer region, in which some of the associated SNPs alter transcription factor binding. We now identify miR-3662 as a new functional driver contributing to the associated phenotypes. The GWAS SNPs are strongly associated with higher miR-3662 expression. Genome editing of rs66650371, a three-base-pair deletion, suggests a functional link between the SNP genotype and the abundance of miR-3662. Increasing miR-3662′s abundance increases colony formation in hematopoietic progenitor cells, particularly the erythroid lineage. In contrast, miR-3662 is not expressed in acute myeloid leukemia cells, and its overexpression has potent antileukemic effects in vitro and in vivo . Mechanistically, miR-3662 directly targets NF-κB–mediated transcription. Thus, miR-3662 is a new player of the hematopoietic 6q23.3 locus.
Significance: The characterization of miR-3662 has identified a new actor in the prominent hematopoietic quantitative trait locus in chromosome 6q23.3. The mechanistic insights into miR-3662′s function may reveal novel or only partially known pathways for normal and malignant hematopoietic cell proliferation. Cancer Discov; 6(9); 1036–51. ©2016 AACR.
This article is highlighted in the In This Issue feature, [p. 932][1]
[1]: /lookup/volpage/6/932?iss=9
14 citations
TL;DR: The NMR solution structure of NRAS isoform 5 is described to be used as a starting point to understand its biophysical interactions and forms a helix‐turn‐coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.
Abstract: It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix-turn-coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.
4 citations
Patent•
12 Feb 2016TL;DR: Compositions comprising therapeutic oligonucleotide miR-3151 compounds that target the expression of genes associated with tumorigenesis or cell transformation are provided in this article, where the authors provide a detailed discussion of their work.
Abstract: Compositions comprising therapeutic oligonucleotide miR-3151 compounds that target the expression of genes associated with tumorigenesis or cell transformation are provided.
TL;DR: Screening all Icelandic individuals diagnosed with colorectal cancer over a decade for dMMR and correlated the results with complete information on LS gene variation and cancer incidence found that LS is associated withincreased cancer risk.
Abstract: 1542Background: Lynch syndrome (LS) is caused by germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) or EPCAM, and is associated withincreased cancer risk. The incidence of LS in Iceland is unknown. We investigated the incidence of LS and etiology of MMR deficiency (dMMR) by screening all Icelandic individuals diagnosed with colorectal cancer (CRC) over a decade for dMMR and correlated the results with complete information on LS gene variation and cancer incidence. Methods: Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 was performed on all CRC cases diagnosed from 2000-2009 in Iceland. Cases with MLH1/PMS2 deficient tumors underwent MLH1 hypermethylation (MLH1-hm) testing. Information on MMR gene variation in the Icelandic population was extracted from a genetic database. Germline genotyping was done on peripheral blood mononuclear cells obtained from all patients with dMMR tumors and 78.2% of patients with MMR proficient tumors. All unexplained dMMR cases underwent whol...
TL;DR: The article to be discussed appeared in the last issue of Cancer Research for 1993, which classifies as the year of colon cancer.
Abstract: See related article by Peltomaki et al., [Cancer Research 1993;53:5853–55][1] .
Visit the Cancer Research 75th Anniversary [timeline][2].
The article to be discussed appeared in the last issue of Cancer Research for 1993 ([1][3]). As it happens, 1993 classifies as the year of colon cancer
01 Jan 2016
TL;DR: It is shown here that muta- tions in the nebulin gene located within this region are associated with the disease, and that nebulin protein is a giant protein found in nemaline bodies.
Abstract: The congenital nemaline myopathies are rare hereditary muscle disorders characterized by the presence in the muscle fibers of nemaline bodies consisting of proteins derived from the Z disc and thin filament. In a single large Australian family with an autosomal dominant form of nemaline myopathy, the disease is caused by a mutation in the a-tropomyosin gene TPM3. The typical form of nemaline myopathy is inherited as an autosomal recessive trait, the locus of which we previously assigned to chromosome 2q21.2-q22. We show here that muta- tions in the nebulin gene located within this region are associated with the disease. The nebulin protein is a giant protein found in