ABSTRACT
BACKGROUND: Advances in cancer genome sequencing have led to the development of various next-generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests carried out in the same patient. METHODS: Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)]. RESULTS: The median time between the diagnosis of stage IV disease and the first genomic test was 23.5 days (0-767), after a median number of 0 (0-3) prior systemic lines of treatment of advanced disease. Most frequent genomic alterations (GA) were found in the genes TP53 (50.0%), TERT promoter (36.3%); ARID1 (29.5%); FGFR2/3 (20.5%), PIK3CA (20.5%) and ERBB2 (18.2%). While we identified GA in both tests, the overall concordance between the two platforms was only 16.4% (0%-50%), and 17.1% (0%-50%) for those patients (n = 6) with both tests conducted around the same time (median difference = 36 days). On the contrary, in the subgroup of patients (n = 5) with repeated NGS in ctDNA after a median of 1 systemic therapy between the two tests, average concordance was 55.5% (12.1%-100.0%). Tumor tissue mutational burden was significantly associated with number of GA in G360 report (P < 0.001), number of known GA (P = 0.009) and number of variants of unknown significance (VUS) in F1 report (P < 0.001), and with total number of GA (non-VUS and VUS) in F1 report (P < 0.001). CONCLUSIONS: This study suggests a significant discordance between clinically available NGS panels in advanced urothelial cancer, even when collected around the same time. There is a need for better understanding of these two possibly complementary NGS platforms for better integration into clinical practice.
Subject(s)
Circulating Tumor DNA/genetics , DNA, Neoplasm/genetics , Urinary Bladder Neoplasms/genetics , Aged , Aged, 80 and over , Circulating Tumor DNA/analysis , Circulating Tumor DNA/blood , DNA, Neoplasm/analysis , DNA, Neoplasm/blood , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Middle Aged , Neoplasm Metastasis , Pilot Projects , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/pathologySubject(s)
Dairying , Fertility/genetics , Insulin-Like Growth Factor II/genetics , Lactation/genetics , Polymorphism, Genetic , Animals , Breeding , Cattle , DNA Mutational Analysis , Exons , Female , Genotype , Male , PolandABSTRACT
Single nucleotide polymorphisms (SNPs) in growth hormone 1 (GH1), insulin-like growth factor 1 (IGF1) and leptin (LEP), all candidates for production traits in cattle, were characterized in North Eurasian cattle breeds. Allele frequencies of IGF1 exhibited significant (P < 0.05) deviation from neutral expectation and therefore, might be associated with divergence in North Eurasian cattle because of genetic selection. Allele frequencies and lower heterozygosity of LEP may indicate a recent introduction of an alternative allele in this geographic region. Locus F(ST) estimates were highest for IGF1 (0.151, sigma = 0.042) and lowest for GH (0.062, sigma = 0.020). Our results suggest a slightly higher population differentiation across the candidate genes (FST = 0.108) than across microsatellites (FST = 0.095), possibly because of selection and stochastic effects.
Subject(s)
Cattle/genetics , Growth Hormone/genetics , Insulin-Like Growth Factor I/genetics , Leptin/genetics , Polymorphism, Single Nucleotide , Animals , Asia , Cattle/classification , Europe , Gene Frequency , Genes , Heterozygote , Microsatellite Repeats , Quantitative Trait LociABSTRACT
New molecular techniques focused on genome analysis open new possibilities for complex evaluation of economically important traits in farm animals. Milk production traits are typical quantitative characteristics controlled by a number of genes. Mutations in their sequences may alter animal performance as well as their breeding values. In this study, we investigated the effect of 3 restriction fragment length polymorphisms (RFLP): HphI, Kpn2I, and Sau3AI in the leptin gene, on bull breeding values for milk, fat, and protein yield, and fat and protein content. One hundred seventeen Polish Black and White AI bulls were genotyped. Pedigree analysis indicated a relatively close relationship between the bulls. Statistical analysis indicated that the HphI polymorphism has a significant effect on milk and protein yield. Animals with the TT genotype had approximately 2x higher estimated breeding values for milk and protein yields. No effect was found for the other 2 polymorphisms.
