Screening
            <i>hCHK2</i>
            for Mutations

Sodha, Nayanta; Williams, Richard; Mangion, Jonathan; Bullock, Sarah; Yuille, Martin; Eeles, Rosalind

doi:10.1126/science.289.5478.359a

Cited by 70 publications

(46 citation statements)

References 3 publications

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“…Furthermore, we demonstrated that JF305 carries a CHK21100delC mutation one of the two mutations identified in Li-Fraumeni syndrome patients and no BRCA1 or BRCA2 mutations (26). This phenomenon is yet to be reported in JF305 and other pancreatic cancer cell lines but has been widely associated with increased risk of breast cancer.…”

Section: Discussionmentioning

confidence: 70%

“…Serine/Threonine kinase domain is located at C terminal and only active during DNA damage [24]. Three founder mutations 1100delC, I157T, and 1422delT were first identified in Li-Fraumeni syndrome patients [25] but 1422delT is a polymorphism in a non-processed Psuedogene [26]. Other CHK2 mutations like S428F, IVS2 +IG > 2 and 5395delC have also been reported in different studies [27]- [30].…”

Section: Introductionmentioning

confidence: 99%

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CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

Ndawula¹,

Yang²,

Gong³

et al. 2014

JBM

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JF305 is a highly prolific pancreatic cancer cell line that originated from a Chinese patient. The cell line bears a functional HR double strand DNA repair mechanism but very responsive to PARP treatment a phenomenon clearly suggesting presence of an anomaly in the mechanism. Brca1, Brca2 and CHK2 proteins are very important constituents of the HR mechanism whose respective gene coding mutations are strongly associated with several cancers and are widely exploited in anticancer chemotherapy. In this current study, the BRCA1, BRCA2 gene mutation status in JF305 was determined together with the presence of 3 widely reported cancer linked CHK2 founder mutations (1100delC, I157T, IVS2 +IG > A). CHK21100delC genotype was determined using allele specific PCR, while the PCR-RFLP assay was used for I157T, IVS2 +IG > A analysis. PCR and direct sequencing were used for assessing the BRCA1 and BRCA2 gene. Results revealed that JF305 is CHK21100delC heterozygous mutant, CHK2I157T and CHK2IVS2 +IG > A wild type. Furthermore, it was observed that JF305 lacked BRCA1 and BRCA2 gene mutations. The mutation status identification of CHK2 and BRCA1/2 in JF305 provides a major milestone towards elucidating the properties of the cell line which subsequently promises to be an excellent model for evaluating the role of parp inhibitors in pancreatic cancer chemotherapy most especially in the respective cancer cell lines without BRCA1 and BRCA2 gene mutations.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

Ndawula¹,

Yang²,

Gong³

et al. 2014

JBM

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“…Primers used for amplification of exons 10 -14, which are known to be repeated on several other chromosomes (Sodha et al, 2000), were designed so that both primers for each primer pair had a base mismatch in the most 3 0 nucleotide, compared with sequences from nonfunctional copies of CHEK2. Genomic DNA was used at 25 ng per 15 ml reaction mixture containing 1.5 mM MgCl 2 ; 20 mM each of dNTP; 0.5 mCi of a( 33 P)-dCTP (Amersham Pharmacia, Uppsala, Sweden); 0.6 mM of each primer; 1.0 U AmpliTaqGold; and the reaction buffer provided by the supplier (PE Biosystems, Foster City, CA, USA).…”

Section: Mutation Screening With Sscp Analysismentioning

confidence: 99%

CHEK2 variants associate with hereditary prostate cancer

et al. 2003

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Recently, variants in CHEK2 gene were shown to associate with sporadic prostate cancer in the USA. In the present study from Finland, we found that the frequency of 1100delC, a truncating variant that abrogates the kinase activity, was significantly elevated among 120 patients with hereditary prostate cancer (HPC) (four out of 120 (3.3%); odds ratio 8.24; 95% confidence interval 1.49 -45.54; P ¼ 0.02) compared to 480 population controls. Suggestive evidence of segregation between the 1100delC mutation and prostate cancer was seen in all positive families. In addition, I157T variant had significantly higher frequency among HPC patients (13 out of 120 (10.8%); odds ratio 2.12; 95% confidence interval 1.06 -4.27; P ¼ 0.04) than the frequency 5.4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level.

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“…To avoid interferences with any of the multiple homologous CHK2 sequences described within the genome, which comprises exons 10 to 14, the probe was specially designed in exon 1. 33 The quantitative assay amplified 100 ng of DNA as template in 2 to 4 replicates, using the Taqman Universal Master Mix, 200 nM of each CHK2 primers and 300 nM of CHK2 probe. Amplification conditions were 2 minutes at 50°C for uracil N-glycosylase (UNG) activation, and 10 minutes at 95°C for TaqGold activation and predenaturation, followed by 40 cycles at 95°C for 15 seconds and 60°C for 1 minute.…”

Section: Real-time Quantitative Pcr Analysis Of Chk2 Genementioning

confidence: 99%

CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas

Tort

Hernández

Beà

et al. 2002

Blood

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Screening hCHK2 for Mutations

Cited by 70 publications

References 3 publications

CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

CHEK2 variants associate with hereditary prostate cancer

CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas

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Screening hCHK2 for Mutations

Cited by 70 publications

References 3 publications

CHK21100delC, I157T, IVS2 +IG &gt; A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

CHK21100delC, I157T, IVS2 +IG &gt; A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

CHEK2 variants associate with hereditary prostate cancer

CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas

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CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line

CHK21100delC, I157T, IVS2 +IG > A, BRCA1 and BRCA2 Mutation Analysis in JF305: A Pancreatic Cancer Cell Line