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Evaluation of the Oncomine Comprehensive Assay v3 panel for the detection of 1p/19q codeletion in oligodendroglial tumours

Ali RH, Alateeqi M, Jama H, Alrumaidhi N, Alqallaf A, Mohammed EM, et al.

J Clin Pathol, 2023 Feb;76(2):103-110.
PMID: 34489310 DOI: 10.1136/jclinpath-2021-207876

AIMS: Accurate assessment of 1p/19q codeletion status in diffuse gliomas is of paramount importance for diagnostic, prognostic and predictive purposes. While targeted next generation sequencing (NGS) has been widely implemented for glioma molecular profiling, its role in detecting structural chromosomal variants is less well established, requiring supplementary informatic tools for robust detection. Herein, we evaluated a commercially available amplicon-based targeted NGS panel (Oncomine Comprehensive Assay v3) for the detection of 1p/19q losses in glioma tissues using an Ion Torrent platform and the standard built-in NGS data analysis pipeline solely.
METHODS: Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard.
RESULTS: The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (p<0.001). NGS was concordant with FISH and was superior to it in distinguishing partial from contiguous losses indicative of whole-arm chromosomal deletion.
CONCLUSIONS: This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH.

Matched MeSH terms: Chromosomes, Human, Pair 1/genetics
Fulltext Crystal structure and functional analysis of human C1ORF123

A Rahaman SN, Mat Yusop J, Mohamed-Hussein ZA, Aizat WM, Ho KL, Teh AH, et al.

PeerJ, 2018;6:e5377.
PMID: 30280012 DOI: 10.7717/peerj.5377

Proteins of the DUF866 superfamily are exclusively found in eukaryotic cells. A member of the DUF866 superfamily, C1ORF123, is a human protein found in the open reading frame 123 of chromosome 1. The physiological role of C1ORF123 is yet to be determined. The only available protein structure of the DUF866 family shares just 26% sequence similarity and does not contain a zinc binding motif. Here, we present the crystal structure of the recombinant human C1ORF123 protein (rC1ORF123). The structure has a 2-fold internal symmetry dividing the monomeric protein into two mirrored halves that comprise of distinct electrostatic potential. The N-terminal half of rC1ORF123 includes a zinc-binding domain interacting with a zinc ion near to a potential ligand binding cavity. Functional studies of human C1ORF123 and its homologue in the fission yeast Schizosaccharomyces pombe (SpEss1) point to a role of DUF866 protein in mitochondrial oxidative phosphorylation.

Matched MeSH terms: Chromosomes, Human, Pair 1
De novo interstitial deletion of 1q32.2-q32.3 including the entire IRF6 gene in a patient with oral cleft and other dysmorphic features

Salahshourifar I, Halim AS, Sulaiman WA, Ariffin R, Naili Muhamad Nor N, Zilfalil BA

Cytogenet Genome Res, 2011;134(2):83-7.
PMID: 21447942 DOI: 10.1159/000325541

Microdeletion of the Van der Woude syndrome (VWS) critical region is a relatively rare event, and only a few cases have been reported in the medical literature. The extent of the deletion and the genotype-phenotype correlation are 2 crucial issues.

Matched MeSH terms: Chromosomes, Human, Pair 1*
FISHing for 1p19q codel in oligodendroglioma

Kong PL, Cheah PL, Mun KS, Chiew SF, Lau TP, Koh CC, et al.

Malays J Pathol, 2020 Dec;42(3):369-376.
PMID: 33361717

Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Matched MeSH terms: Chromosomes, Human, Pair 1/genetics*
Fulltext Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

Horne HN, Chung CC, Zhang H, Yu K, Prokunina-Olsson L, Michailidou K, et al.

PLoS One, 2016;11(8):e0160316.
PMID: 27556229 DOI: 10.1371/journal.pone.0160316

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

Matched MeSH terms: Chromosomes, Human, Pair 1*
Fulltext Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, et al.

Oncotarget, 2016 Oct 11;7(41):66328-66343.
PMID: 27579533 DOI: 10.18632/oncotarget.11041

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Matched MeSH terms: Chromosomes, Human, Pair 1/genetics*
Fulltext Demarcation of informative chromosomes in tropical sweet corn inbred lines using microsatellite DNA markers

Kashiani P, Saleh G, Panandam JM, Abdullah NA, Selamat A

Genet Mol Biol, 2012 Jul;35(3):614-21.
PMID: 23055801 DOI: 10.1590/S1415-47572012000400012

A study of genetic variation among 10 pairs of chromosomes extracted from 13 tropical sweet corn inbred lines, using 99 microsatellite markers, revealed a wide range of genetic diversity. Allelic richness and the number of effective alleles per chromosome ranged from 2.78 to 4.33 and 1.96 to 3.47, respectively, with respective mean values of 3.62 and 2.73. According to the Shannon's information index (I) and Nei's gene diversity coefficient (Nei), Chromosome 10 was the most informative chromosome (I = 1.311 and Nei = 0.703), while Chromosome 2 possessed the least (I = 0.762 and Nei = 0.456). Based on linkage disequilibrium (LD) measurements for loci less than 50 cM apart on the same chromosome, all loci on Chromosomes 1, 6 and 7 were in equilibrium. Even so, there was a high proportion of genetic variation in Chromosomes 4, 5, 8, 9 and 10, thereby revealing their appropriateness for use in the genetic diversity investigations among tropical sweet corn lines. Chromosome 4, with the highest number of loci in linkage disequilibrium, was considered the best for marker-phenotype association and QTL mapping, followed by Chromosomes 5, 8, 9 and 10.

Matched MeSH terms: Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 10
Fulltext Meta-Analysis of Quantitative Traits Loci (QTL) Identified in Drought Response in Rice (Oryza sativa L.)

Selamat N, Nadarajah KK

Plants (Basel), 2021 Apr 07;10(4).
PMID: 33917162 DOI: 10.3390/plants10040716

Rice is an important grain that is the staple food for most of the world's population. Drought is one of the major stresses that negatively affects rice yield. The nature of drought tolerance in rice is complex as it is determined by various components and has low heritability. Therefore, to ensure success in breeding programs for drought tolerant rice, QTLs (quantitative trait loci) of interest must be stable in a variety of plant genotypes and environments. This study identified stable QTLs in rice chromosomes in a variety of backgrounds and environments and conducted a meta-QTL analysis of stable QTLs that have been reported by previous research for use in breeding programs. A total of 653 QTLs for drought tolerance in rice from 27 genetic maps were recorded for analysis. The QTLs recorded were related to 13 traits in rice that respond to drought. Through the use of BioMercartor V4.2, a consensus map containing QTLs and molecular markers were generated using 27 genetic maps that were extracted from the previous 20 studies and meta-QTL analysis was conducted on the consensus map. A total of 70 MQTLs were identified and a total of 453 QTLs were mapped into the meta-QTL areas. Five meta-QTLs from chromosome 1 (MQTL 1.5 and MQTL 1.6), chromosome 2 (MQTL2.1 and MQTL 2.2) and chromosome 3 (MQTL 3.1) were selected for functional annotation as these regions have high number of QTLs and include many traits in rice that respond to drought. A number of genes in MQTL1.5 (268 genes), MQTL1.6 (640 genes), MQTL 2.1 (319 genes), MQTL 2.2 (19 genes) and MQTL 3.1 (787 genes) were annotated through Blast2GO. Few major proteins that respond to drought stress were identified in the meta-QTL areas which are Abscisic Acid-Insensitive Protein 5 (ABI5), the G-box binding factor 4 (GBF4), protein kinase PINOID (PID), histidine kinase 2 (AHK2), protein related to autophagy 18A (ATG18A), mitochondrial transcription termination factor (MTERF), aquaporin PIP 1-2, protein detoxification 48 (DTX48) and inositol-tetrakisphosphate 1-kinase 2 (ITPK2). These proteins are regulatory proteins involved in the regulation of signal transduction and gene expression that respond to drought stress. The meta-QTLs derived from this study and the genes that have been identified can be used effectively in molecular breeding and in genetic engineering for drought resistance/tolerance in rice.

Matched MeSH terms: Chromosomes, Human, Pair 1
Fulltext Abnormalities of chromosome 11Q in three cases of acute myeloid leukemia

Ten SK, Khor MK, Khalid H, Lin HP, Ng SC, Cheong SK, et al.

Singapore Med J, 1992 Apr;33(2):164-6.
PMID: 1621121

The haematological findings and case history of 3 patients with the association of acute myeloid leukemia and translocation involving the long arm of chromosome no. 11 are presented. The recipient chromosome for the translocated material from chromosome 11 differs in all the three cases being namely chromosomes 1, 10 and 17.

Matched MeSH terms: Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11*; Chromosomes, Human, Pair 17
Early transition from insulin to sulfonylureas in neonatal diabetes and follow-up: Experience from China

Li X, Xu A, Sheng H, Ting TH, Mao X, Huang X, et al.

Pediatr Diabetes, 2018 03;19(2):251-258.
PMID: 28791793 DOI: 10.1111/pedi.12560

BACKGROUND: Sulfonylurea therapy can improve glycemic control and ameliorate neurodevelopmental outcomes in patients suffering from neonatal diabetes mellitus (NDM) with KCNJ11 or ABCC8 mutations. As genetic testing results are often delayed, it remains controversial whether sulfonylurea treatment should be attempted immediately at diagnosis or doctors should await genetic confirmation.
OBJECTIVE: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available.
METHODS: The medical records of NDM patients with their follow-up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient.
RESULTS: There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14-120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3-0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2-0.4 mg/kg/d). No serious adverse events were reported.
CONCLUSIONS: Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM.

Matched MeSH terms: Chromosomes, Human, Pair 1/genetics
Fulltext Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

Cai Q, Zhang B, Sung H, Low SK, Kweon SS, Lu W, et al.

Nat Genet, 2014 Aug;46(8):886-90.
PMID: 25038754 DOI: 10.1038/ng.3041

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

Matched MeSH terms: Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 15

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