Discovering moderate-risk breast cancer susceptibility genes

Hollestelle, Antoinette; Wasielewski, Marijke; Martens, John W.M.; Schutte, Mieke

doi:10.1016/j.gde.2010.02.009

Cited by 93 publications

(90 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In pre-cancerous lesions, both the ATM and ATR pathways are activated, thereby helping the cell to mount a resistance to tumor development (Gorgoulis et al, 2005;Negrini et al, 2010). In addition, loss-of-function mutations or deletions of ATM or ATR, as well as their reduced kinase activity or expression levels, or deletions of components of their downstream pathways, all promote cell survival and result in a multi-fold increase in the propensity of a cell to become cancerous, and in an acceleration of tumor progression (Nevanlinna and Bartek, 2006;Spring et al, 2002;Vahteristo et al, 2002;Bertoni et al, 1999;Greenman et al, 2007;Guarini et al, 2012;Hollestelle et al, 2010;Menoyo et al, 2001;Reiman et al, 2011;Renwick et al, 2006;Roberts et al, 2012;Squatrito et al, 2010;Tanaka et al, 2012;Zighelboim et al, 2015Zighelboim et al, , 2009) (see poster). In particular, in ATM, distinct mutations have been found that cause different human malignancies, including lung cancer, breast cancer, colon cancer, lymphocytic leukemia, pancreatic cancer, and head and neck cancer, among others (Ding et al, 2008;Goldgar et al, 2011;Guarini et al, 2012;Roberts et al, 2012;Seshagiri et al, 2012) (see poster).…”

Section: Box 1 Relevance Of Atm and Atr Signaling In Cancermentioning

confidence: 99%

ATM and ATR signaling at a glance

Awasthi

Foiani

Kumar

2015

Journal of Cell Science

232

228

View full text Add to dashboard Cite

There was an error published in J. Cell Sci. 128, 4255-4262.An incorrect citation and reference was given for the last sentence in Box 2. The correct citation and reference are: A recent review provides a detailed update on ATM and ATR inhibitors, and their potential as drug targets (Weber and Ryan, 2015).Weber, A.M. and Ryan, A.J. (2015). ATM and ATR as therapeutic targets in cancer. Pharmacol Ther. 149, 124-138.The authors apologise to the readers for any confusion that this error might have caused. Although the role of both ATM and ATR in DNA repair, cell cycle regulation and apoptosis have been well studied, both still remain in the focus of current research activities owing to their role in cancer. Recent advances in the field suggest that these proteins have an additional function in maintaining cellular homeostasis under both stressed and non-stressed conditions. In this Cell Science at a Glance article and the accompanying poster, we present an overview of recent advances in ATR and ATM research with emphasis on that into the modes of ATM and ATR activation, the different signaling pathways they participate in -including those that do not involve DNA damage -and highlight their relevance in cancer. 1285

show abstract

Section: Box 1 Relevance Of Atm and Atr Signaling In Cancermentioning

confidence: 99%

ATM and ATR signaling at a glance

Awasthi

Foiani

Kumar

2015

Journal of Cell Science

232

228

View full text Add to dashboard Cite

show abstract

“…In other geographical areas the mutation is much rarer or even absent. [3][4][5] The 1100delC frameshift mutation causes a premature stop codon, which triggers nonsense-mediated decay, resulting in a lower expression of CHEK2 mRNA in heterozygous carriers. [6][7][8] Although a low level of mutant mRNA remains detectable, the presence of the mutated protein could not be demonstrated in lymphoblastoid cell lines from humans heterozygous for the 1100delC mutation.…”

Section: Introductionmentioning

confidence: 99%

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

et al. 2013

Self Cite

View full text Add to dashboard Cite

The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4-32.6, P ¼ 0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.

show abstract

“…Further, genetic linkage analyses failed to identify additional high-penetrance susceptibility genes and the identification of rare variants of genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2 in families lacking BRCA mutations (Meijers-Heijboer et al, 2002;Thompson et al, 2005;Rahman et al, 2007;Hollestelle et al, 2010), associated with a moderate risk of disease, can explain only a small portion of familial risk.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer genome-wide association studies: there is strength in numbers

et al. 2011

View full text Add to dashboard Cite

Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-specific protein 1 (LSP1). The most strongly associated SNP was in intron 2 of the FGFR2 gene that is amplified and overexpressed in 5-10% of BC. rs3803662 of TNRC9 gene has been shown to be the SNP with the strongest association with BC, in particular, this polymorphism seems to be correlated with bone metastases and estrogen receptor positivity. Relevant data indicate that SNP rs889312 in MAP3K1 is correlated with BC susceptibility only in BRCA2 mutation carriers, but is not associated with an increased risk in BRCA1 carriers. Finally, different SNPs in LSP1 and H19 and in minor genes probably were associated with BC risk. New susceptibility allelic variants associated with BC risk were recently discovered including potential causative genes involved in regulation of cell cycle, apoptosis, metabolism and mitochondrial functions. In conclusion, the identification of disease susceptibility loci may lead to a better understanding of the biological mechanism for BC to improve prevention, early detection and treatment.

show abstract

Discovering moderate-risk breast cancer susceptibility genes

Cited by 93 publications

References 51 publications

ATM and ATR signaling at a glance

ATM and ATR signaling at a glance

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

Breast cancer genome-wide association studies: there is strength in numbers

Contact Info

Product

Resources

About