scholarly journals Copy Number Profiles of Prostate Cancer in Men of Middle Eastern Ancestry

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2363
Author(s):  
Alia Albawardi ◽  
Julie Livingstone ◽  
Saeeda Almarzooqi ◽  
Nallasivam Palanisamy ◽  
Kathleen E. Houlahan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Middle Eastern ◽  
Chromosome 1 ◽  
Glutathione S Transferase ◽  
Iq Motif ◽  
Genome Wide ◽  
Gene Level ◽  
Somatic Amplification

Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of genome-wide copy number profiles of 401 tumors of all ancestries. FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (2.3%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 × 10−3). Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those in men of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (two-sided proportion test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ motif-containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Larger studies investigating ME populations are warranted to confirm these observations.

scholarly journals Molecular Profiles of Prostate Cancer in Men of Middle Eastern Ancestry Identifies Key Differences with Western Populations: A Multiethnic SNP Array Study

2021 ◽  
Author(s):  
Alia Albawardi ◽  
Julie Livingstone ◽  
Saeeda Al Marzooqi ◽  
Kathleen Houlahan ◽  
Aktham Adnan Ahmad Awwad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Outcome Measurement ◽  
Middle Eastern ◽  
Snp Array ◽  
Good Prognosis ◽  
Chromosome 1 ◽  
Glutathione S Transferase ◽  
Iq Motif ◽  
Somatic Amplification

Background: Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. Design, setting and participants: To characterize genomic differences between ME, EUR, ASN and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletions and MYC amplification was carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of copy number profiles of 401 tumors of all ancestries. Outcome measurement and statistical analysis: FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. Results and Limitation: NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (0.23%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 x 10-3). No differences in MYC amplifications was noted between the two cohorts using array-based CNAs. Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (Proportions test; Q &lt; 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ Motif Containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Conclusion: Significant differences in genetic background exists between different ancestries. The lower number of somatic CNAs observed in prostate cancer arising in men of ME ancestry may explain the relatively good prognosis in this population. Larger studies are warranted.

scholarly journals LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci

2021 ◽  
Author(s):  
Luca Comai ◽  
Kirk R Amundson ◽  
Benny Ordonez ◽  
Xin Zhao ◽  
Guilherme Tomaz Braz ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Large Scale ◽  
Chromosomal Translocations ◽  
Chromosome 1 ◽  
Structural Variations ◽  
Painting Probes ◽  
Two Populations

Large scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1Mb bin, we tested linkage disequilibrium with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a non-reciprocal translocation between chromosome 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. Alca Tarma the terminal arm of chromosome 4 translocated to the tip of chromosome 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, but we identified pericentromeric LD suggesting the effect of repeats. This method should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.

scholarly journals Amplification of the EGFR and CCND1 Are Coordinated and Play Important Roles in the Progression of Oral Squamous Cell Carcinomas

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 760 ◽  
Author(s):  
Huei-Tzu Chien ◽  
Sou-De Cheng ◽  
Chun-Ta Liao ◽  
Hung-Ming Wang ◽  
Shiang-Fu Huang
Keyword(s):  
Squamous Cell ◽  
Tumor Suppressor Genes ◽  
Copy Number ◽  
Clinical Stage ◽  
Copy Number Alterations ◽  
Suppressor Genes ◽  
Common Cancer ◽  
Genome Wide

Oral squamous cell carcinoma (OSCC) is a common cancer in Taiwan and worldwide. To provide some clues for clinical management of OSCC, 72 advanced-stage OSCCs were analyzed using two microarray platforms (26 cases with Affymetrix 500 K and 46 cases with Affymetrix SNP 6.0). Genomic identification of significant targets in cancer analyses were used to identify significant copy number alterations (CNAs) using a q-value cutoff of 0.25. Among the several significant regions, 12 CNAs were common between these two platforms. Two gain regions contained the well-known oncogenes EGFR (7p11.2) and CCND1 (11q13.3) and several known cancer suppressor genes, such as FHIT (3p14.2–p12.1), FAT1 (4q35.1), CDKN2A (9p21.3), and ATM (11q22.3–q24.3), reside within the 10 deletion regions. Copy number gains of EGFR and CCND1 were further confirmed by fluorescence in situ hybridization and TaqMan CN assay, respectively, in 257 OSCC cases. Our results indicate that EGFR and CCND1 CNAs are significantly associated with clinical stage, tumor differentiation, and lymph node metastasis. Furthermore, EGFR and CCND1 CNAs have an additive effect on OSCC tumor progression. Thus, current genome-wide CNA analysis provides clues for future characterization of important oncogenes and tumor suppressor genes associated with the behaviors of the disease.

Genome-wide copy number analysis reveals candidate gene loci that confer susceptibility to high-grade prostate cancer

2017 ◽  
Vol 35 (9) ◽  
pp. 545.e1-545.e11 ◽  
Author(s):  
Prevathe Poniah ◽  
Shamsul Mohd Zain ◽  
Azad Hassan Abdul Razack ◽  
Shanggar Kuppusamy ◽  
Shankar Karuppayah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Candidate Gene ◽  
Copy Number ◽  
High Grade ◽  
Copy Number Analysis ◽  
Genome Wide

High-resolution genome-wide copy-number analysis suggests a monoclonal origin of multifocal prostate cancer

2012 ◽  
Vol 51 (6) ◽  
pp. 579-589 ◽  
Author(s):  
Lara K. Boyd ◽  
Xueying Mao ◽  
Liyan Xue ◽  
Dongmei Lin ◽  
Tracy Chaplin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Resolution ◽  
Copy Number ◽  
Copy Number Analysis ◽  
Genome Wide

scholarly journals Genome-wide association study of germline copy number variations reveals an association with prostate cancer aggressiveness

Mutagenesis ◽  
2020 ◽  
Vol 35 (3) ◽  
pp. 283-290
Author(s):  
Stefanie Brezina ◽  
Moritz Feigl ◽  
Tanja Gumpenberger ◽  
Ricarda Staudinger ◽  
Andreas Baierl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Risk Stratification ◽  
Cancer Patients ◽  
Copy Number ◽  
Copy Number Variations ◽  
Prostatic Hyperplasia ◽  
Aggressive Prostate Cancer ◽  
Genome Wide ◽  
Cancer Aggressiveness

Abstract Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.

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