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Analysis of 11q21-24 loss of heterozygosity candidate target genes in breast cancer: indications of TSLC1 promoter hypermethylation.

https://arctichealth.org/en/permalink/ahliterature19019
Source
Genes Chromosomes Cancer. 2002 Aug;34(4):384-9
Publication Type
Article
Date
Aug-2002
Author
Minna Allinen
Liisa Peri
Sonja Kujala
Jaana Lahti-Domenici
Kati Outila
Sanna-Maria Karppinen
Virpi Launonen
Robert Winqvist
Author Affiliation
Department of Clinical Genetics, University Hospital, University of Oulu, FIN-90029 OYS, Oulu, Finland.
Source
Genes Chromosomes Cancer. 2002 Aug;34(4):384-9
Date
Aug-2002
Language
English
Publication Type
Article
Keywords
Breast Neoplasms - genetics
Cell Cycle Proteins
Chromosomes, Human, Pair 11 - genetics
CpG Islands - genetics
DNA Methylation
DNA Mutational Analysis - methods
DNA-Binding Proteins - genetics
Female
Genes, Tumor Suppressor
Humans
Immunoglobulins
Loss of Heterozygosity - genetics
Membrane Proteins
Neoplasm Proteins - genetics
Promoter Regions (Genetics) - genetics
Protein Kinases - genetics
Protein-Serine-Threonine Kinases - genetics
Proteins - genetics
Research Support, Non-U.S. Gov't
Tumor Suppressor Proteins
Abstract
Loss of heterozygosity (LOH) at the distal half of chromosome arm 11q is frequent in a variety of human tumors, including breast cancer, and is often associated with poor prognosis. In an ongoing attempt to locate and characterize the main target genes within this chromosome region, we first looked for aberrations in known genes either suggested to be involved in tumorigenesis or shown to suppress tumor formation. We examined 31 primary breast tumors showing LOH in 11q21-24 for mutations in the MRE11A, CHK1, PPP2R1B, and TSLC1 genes. The absence of intragenic alterations related to cancer led us next to evaluate possible gene silencing resulting from promoter region CpG hypermethylation, using the bisulfite sequencing technique. In addition to the four genes mentioned above, we also analyzed the ATM gene, which had been investigated for certain germline mutations in an earlier study. Only the TSLC1 promoter region exhibited aberrant methylation patterns, and altogether 33% (10/30) of the successfully analyzed tumors showed evidence of elevated levels of TSLC1 CpG methylation. Ten percent (3/30) of the tumors showed significantly increased methylation. Thus, as has been shown in lung and some other forms of cancer, hypermethylation of the TSLC1 promoter region is also frequently a second hit along with LOH in breast cancer.
PubMed ID
12112527 View in PubMed
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[Analysis of BRCA1/2 and CHEK2 mutations in ovarian cancer and primary multiple tumors involving the ovaries. Patients of Russian population using biochips].

https://arctichealth.org/en/permalink/ahliterature164485
Source
Mol Biol (Mosk). 2007 Jan-Feb;41(1):37-42
Publication Type
Article
Author
O E Fedorova
L N Liubchenko
Iu G Paiadini
T P Kazubskaia
F A Amosenko
R F Gar'kavtseva
A S Zasedatelev
T V Nasedkina
Source
Mol Biol (Mosk). 2007 Jan-Feb;41(1):37-42
Language
Russian
Publication Type
Article
Keywords
Adult
Aged
BRCA1 Protein - genetics
BRCA2 Protein - genetics
Checkpoint Kinase 2
Female
Gene Frequency
Genetics, Population
Humans
Middle Aged
Mutation
Neoplasms, Multiple Primary - genetics - pathology
Oligonucleotide Array Sequence Analysis - methods
Ovarian Neoplasms - genetics - pathology
Protein-Serine-Threonine Kinases - genetics
Risk factors
Russia
Abstract
Ovarian cancer (OC) is one of the leading cause of cancer death in women. Inherited BRCA1 and BRCA2 mutations strikingly increase OC risk (with lifetime risk estimates ranging at 10-60%). Mutation 1100delC in CHEK2 gene was shown to be associated with breast cancer in women carrying this mutation. Knowledge of the nature and frequency of population-specific mutations in these genes is a critical step in the development of simple and inexpensive diagnostic approaches to DNA analysis. The frequencies of 185delAG, 300T>G, 4153delA, 4158A>G, 5382insC mutations in BRCA1 gene, 695insT and 6174delT mutations in BRCA2 gene and 1100delC mutation in CHEK2 gene were analyzed using biochips in Russian OC patients. We studied 68 women who received a diagnosis of epithelial OC and 19 women with primary multiple tumors involving the ovaries. The 185delAG, 300T>G, 4153delA and 5382insC in BRCA1 gene were identified. The most prevailing mutation was 5382insC in BRCA1 gene (87.5% of all BRCA1 mutations OC patients, 50.0% in patients with primary multiple tumors involving the ovaries). No mutations in BRCA2 and CHEK2 genes were detected.
PubMed ID
17380889 View in PubMed
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Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder.

https://arctichealth.org/en/permalink/ahliterature169433
Source
Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):374-82
Publication Type
Article
Date
Jun-5-2006
Author
Nicholas Barden
Mario Harvey
Bernard Gagné
Eric Shink
Monique Tremblay
Catherine Raymond
Michel Labbé
André Villeneuve
Denis Rochette
Lise Bordeleau
Herbert Stadler
Florian Holsboer
Bertram Müller-Myhsok
Author Affiliation
Neuroscience, CHUL Research Centre and Université Laval, Quebec, Canada. barden@crchul.ulaval.ca
Source
Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):374-82
Date
Jun-5-2006
Language
English
Publication Type
Article
Keywords
Alleles
Bipolar Disorder
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Case-Control Studies
Chromosomes, Human, Pair 12 - genetics
Family Health
Female
France - ethnology
Gene Frequency
Genetic Predisposition to Disease - genetics
Genotype
Humans
Linkage Disequilibrium
Male
Mutation
Pedigree
Polymorphism, Single Nucleotide
Protein-Serine-Threonine Kinases - genetics
Quebec
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2X4
Receptors, Purinergic P2X7
Abstract
Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers on chromosome 12, D12S86 and D12S378, was the most probable genomic region to contain a susceptibility gene for affective disorders. Association studies with microsatellite markers using a case/control sample from the same population (n = 427) revealed significant allelic associations between the bipolar phenotype and marker NBG6. Since this marker is located in intron 9 of the P2RX7 gene, we analyzed the surrounding genomic region for the presence of polymorphisms in regulatory, coding and intron/exon junction sequences. Twenty four (24) SNPs were genotyped in a case/control sample and 12 SNPs in all pedigrees used for linkage analysis. Allelic, genotypic or family-based association studies suggest the presence of two susceptibility loci, the P2RX7 and CaMKK2 genes. The strongest association was observed in bipolar families at the non-synonymous SNP P2RX7-E13A (rs2230912, P-value = 0.000708), which results from an over-transmission of the mutant G-allele to affected offspring. This Gln460Arg polymorphism occurs at an amino acid that is conserved between humans and rodents and is located in the C-terminal domain of the P2X7 receptor, known to be essential for normal P2RX7 function.
PubMed ID
16673375 View in PubMed
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[A PARK8 form of Parkinson's disease: a mutational analysis of the LRRK2 gene in Russian population].

https://arctichealth.org/en/permalink/ahliterature157964
Source
Zh Nevrol Psikhiatr Im S S Korsakova. 2007;107(3):46-50
Publication Type
Article
Date
2007
Author
M I Shadrina
S N Illarioshkin
G Kh Bagyeva
E V Bespalova
T B Zagorodskaia
P A Slominskii
E D Markova
S A Kliushnikov
S A Limborskaia
I A Ivanova-Smolenskaia
Source
Zh Nevrol Psikhiatr Im S S Korsakova. 2007;107(3):46-50
Date
2007
Language
Russian
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
DNA - genetics
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Male
Middle Aged
Mutation
Parkinson Disease - epidemiology - genetics
Polymerase Chain Reaction
Population Surveillance
Prevalence
Protein-Serine-Threonine Kinases - genetics
Russia - epidemiology
Abstract
A recently described form of Parkinson's disease - PARK8 - is caused by mutations in the novel LRRK2 gene on chromosome 12q12. The most common mutation in this gene is the substitution G2019S and we studied it for the first time in a large group of Russian Slavonic patients (311 patients) with Parkinson's disease including 295 sporadic and 16 familial cases. The mutation LRRK2-G2019S was identified in 1% of patients examined (3 cases) and was not found in a group of population control. The clinical picture of all patients with the LRRK2-G2019S mutation was typical for levodopa-responsive parkinsonism and age of disease onset varied widely (from 39 to 71 years). Two different PARK8-linked haplotypes were found in carriers of the mutation that suggested the independent origin of the G2019S mutation on different chromosomes. The identification of mutations in the LRRK2 gene in patients with "ordinary" sporadic Parkinson's disease has serious implications for medical genetic counseling and prognosis in respective families.
PubMed ID
18379513 View in PubMed
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[Apoptosis of peripheral blood lymphocytes in patients with LRRK2-assoctated Parkinson's disease].

https://arctichealth.org/en/permalink/ahliterature124582
Source
Tsitologiia. 2012;54(1):44-8
Publication Type
Article
Date
2012
Author
T S Usenko
A K Emel'ianov
A F Iakimovskii
N A Bogan'kova
T V Vavilova
A L Shvartsman
S N Pchelina
Source
Tsitologiia. 2012;54(1):44-8
Date
2012
Language
Russian
Publication Type
Article
Keywords
Aged
Antigens, CD95 - genetics
Apoptosis - genetics
Case-Control Studies
DNA Mutational Analysis
Female
Flow Cytometry
Humans
Lymphocytes - metabolism - pathology
Male
Middle Aged
Mutation
Parkinson Disease - genetics - pathology
Protein-Serine-Threonine Kinases - genetics
Proto-Oncogene Proteins c-bcl-2 - genetics
Real-Time Polymerase Chain Reaction
Russia
Abstract
Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Although the precise physiological and pathological role of LRRK2 is unclear, a direct link between mutant LRRK2 and apoptosis has been suggested. Using flow cytometric analysis (PI+Annexin V(FITC)) we showed increased spontaneous apoptosis of peripheral blood lymphocytes in patients with LRRK.2-associated PD compared to controls after 24 (P
PubMed ID
22567899 View in PubMed
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Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications.

https://arctichealth.org/en/permalink/ahliterature107374
Source
JAMA Neurol. 2013 Nov;70(11):1359-66
Publication Type
Article
Date
Nov-2013
Author
Nancy J Butcher
Tim-Rasmus Kiehl
Lili-Naz Hazrati
Eva W C Chow
Ekaterina Rogaeva
Anthony E Lang
Anne S Bassett
Author Affiliation
Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada2Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Source
JAMA Neurol. 2013 Nov;70(11):1359-66
Date
Nov-2013
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Aged
Brain - metabolism - pathology
Canada
Chromosome Deletion
DNA-Binding Proteins - metabolism
DiGeorge Syndrome - complications - genetics - pathology
Female
Genetic Testing
Humans
Male
Middle Aged
Mutation - genetics
Neurologic Examination
Observational Study as Topic
Parkinson Disease - complications - genetics - pathology
Protein-Serine-Threonine Kinases - genetics
Severity of Illness Index
Tyrosine 3-Monooxygenase
Young Adult
alpha-Synuclein - metabolism
Abstract
Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition.
To evaluate a possible association between 22q11.2 deletions and PD.
An observational study of the occurrence of PD in the world's largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1-68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder.
A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0-178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical a-synuclein-positive Lewy bodies were present in the expected distribution in 2 cases but absent in another.
These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD.
Notes
Comment In: JAMA Neurol. 2013 Nov;70(11):1355-624018918
PubMed ID
24018986 View in PubMed
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Association of common ATM polymorphism with bilateral breast cancer.

https://arctichealth.org/en/permalink/ahliterature17156
Source
Int J Cancer. 2005 Aug 10;116(1):69-72
Publication Type
Article
Date
Aug-10-2005
Author
Katri Heikkinen
Katrin Rapakko
Sanna-Maria Karppinen
Hannele Erkko
Pentti Nieminen
Robert Winqvist
Author Affiliation
Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland.
Source
Int J Cancer. 2005 Aug 10;116(1):69-72
Date
Aug-10-2005
Language
English
Publication Type
Article
Keywords
Breast Neoplasms - genetics
Cell Cycle Proteins - genetics
DNA Mutational Analysis
DNA-Binding Proteins - genetics
Family Health
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Mutation
Ovarian Neoplasms - genetics
Polymorphism, Genetic
Protein-Serine-Threonine Kinases - genetics
Research Support, Non-U.S. Gov't
Tumor Suppressor Proteins - genetics
Abstract
The ATM kinase has an essential role in maintaining genomic integrity. Loss of both ATM alleles results in ataxia-telangiectasia (A-T), a rare autosomal recessive neuroimmunologic disorder associated with cancer susceptibility. Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for malignancy, in particular, female breast cancer. In the current study, a full mutation analysis of the ATM gene was carried out in patients from 121 breast or breast-ovarian cancer families. We discovered that the combination of 5557G-->A in cis position with IVS38-8 T-->C was associated with bilateral breast cancer (OR = 10.2; 95% CI = 3.1-33.8; p = 0.001). As the 5557G-->A change has been reported to affect an exonic splicing enhancer, we hypothesized that the observed composite allele could have some effect on the correct splicing of exon 39. However, no aberrant transcripts were detected, but ATM expression levels of lymphoblast cell lines from heterozygous carriers of this combination allele were lower than from noncarriers (p = 0.09). Lowered gene expression levels may have direct influence on the activities in DNA damage recognition and response pathways, as well as other genome integrity maintenance functions. Based on the results, we propose a cancer risk-modifying effect for the ATM 5557G-->A, IVS38-8T-->C composite allele.
PubMed ID
15756685 View in PubMed
Less detail

ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia.

https://arctichealth.org/en/permalink/ahliterature174904
Source
Hum Mutat. 2005 Jun;25(6):593
Publication Type
Article
Date
Jun-2005
Author
Geoff W Birrell
Katherine Kneebone
Michael Nefedov
Elena Nefedova
M N Jartsev
Midori Mitsui
Richard A Gatti
Martin F Lavin
Author Affiliation
Department of Cancer and Cell Biology, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane, 4029, Australia. geoffB@qimr.edu.au
Source
Hum Mutat. 2005 Jun;25(6):593
Date
Jun-2005
Language
English
Publication Type
Article
Keywords
Adolescent
Ataxia Telangiectasia - genetics - immunology
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins - genetics
Child
Child, Preschool
DNA-Binding Proteins - genetics
Haplotypes - genetics
Humans
Infant
Mutation - genetics
Protein-Serine-Threonine Kinases - genetics
Russia
Tumor Suppressor Proteins - genetics
Abstract
Mutations in the ATM gene are responsible for the autosomal recessive disorder, ataxia telangiectasia (A-T). Mutations in different ethnic groups are distributed along the entire length of the large, 66 exon ATM gene. In this study, A-T patients from 16 Russian families were assessed for immunological status and ATM haplotype analysis, and screened for ATM mutations. Haplotype analysis was performed to enhance the efficiency of mutation detection. Mutations predicted to cause disease were identified in 19 of 32 alleles (59%), including a truncating mutation (c.5932G>T) that was identified in 8/32 (25%) alleles both by haplotype analysis and mutation screening. This mutation has been found in low abundance in other European A-T cohorts suggesting that this founder-effect mutation may be of Russian origin. The abundance of this mutation may allow for large-scale screening of cancer patients to help clarify the role of ATM in breast and other cancers. Nine of the remaining mutations were previously unreported, and add to the multitude of unique mutations found throughout the gene.
PubMed ID
15880721 View in PubMed
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83 records – page 1 of 9.