6 research outputs found
Genome-wide association study identifies two susceptibility loci for osteosarcoma
Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP
microarray intensity data of 38,303 women from cancer genome-wide association studies
(20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%)
women. Here we show rates for X-chromosome mosaicism are four times higher than mean
autosomal rates; X mosaic events more often include the entire chromosome and participants
with X events more likely harbour autosomal mosaic events. X mosaicism frequency
increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and
autosomes. Methylation array analyses of 33 women with X mosaicism indicate events
preferentially involve the inactive X chromosome. Our results provide further evidence that
the sex chromosomes undergo mosaic events more frequently than autosomes, which could
have implications for understanding the underlying mechanisms of mosaic events and their
possible contribution to risk for chronic diseases
Detectable clonal mosaicism and its relationship to aging and cancer
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases
Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients
Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and
are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study
(GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523
patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR)
and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease
Genome-wide association study identifies two susceptibility loci for osteosarcoma
Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma
Detectable clonal mosaicism and its relationship to aging and cancer
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases