The Wei Group published an article in Cell with a title “Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus”. The authors are: Gao P, Xia JH, Sipeky C, Dong XM, Zhang Q, Yang Y, Zhang P, Cruz SP, Zhang K, Zhu J, Lee HM, Suleman S, Giannareas N, Liu S; PRACTICAL Consortium, Tammela TL, Auvinen A, Wang X, Huang Q, Wang L, Manninen A, Vaarala MH, Wang L, Schleutker J, Wei GH.
In their study they show that a non-coding risk allele associated with aggressive prostate cancer creates a transcription factor binding site that in turn promotes oncogenesis by impacting expression of nearby genes. These results lay the groundwork for translating this finding to the clinic.
For more information: https://www.sciencedirect.com/journal/cell/vol/174/issue/3
The Karppinen group published an article in Journal of Molecular Biology by authors Laukka T, Myllykoski M, Looper RE, Koivunen P. The title of the article is “Cancer-associated 2-oxoglutarate analogues modify histone methylation by inhibiting histone lysine demethylases”.
Histone lysine demethylases (KDMs) are 2-oxoglutarate-dependent dioxygenases (2-OGDDs) that regulate gene expression by altering chromatin structure. Their dysregulation has been associated with many cancers. In this study they conclude that KDM catalytic activity is susceptible to inhibition by tumorigenic 2-OG analogues and suggest that the inhibition of KDMs is involved in the disease mechanism of cancers in which these compounds accumulate, such as the isocitrate dehydrogenase mutations.
For more information: https://www.ncbi.nlm.nih.gov/pubmed/29981745
The Winqvist group, with Pylkäs as the last author, published an article in International Journal of Cancer. The title is “Rare missense mutations in RECQL and POLG associate with inherited predisposition to breast cancer” by Tervasmäki A, Mantere T, Hartikainen JM, Kauppila S, Lee HM, Koivuluoma S, Grip M, Karihtala P, Jukkola-Vuorinen A, Mannermaa A, Winqvist R, Pylkäs K.
Several known breast cancer susceptibility genes with moderate‐to‐high risk alleles encode proteins involved in DNA damage response (DDR). As these explain less than half of the hereditary breast cancer cases, additional predisposing alleles are likely to be discovered. To identify novel susceptibility factors, the authors have systematically analyzed the data from parallel sequencing of 796 DDR genes in 189 Northern Finnish hereditary breast cancer patients for rare missense variants, predicted as deleterious. Two missense variants in genes involved in DNA replication showed significant association with risk of breast cancer: RECQL p.I156M and POLG p.L392V, the former involving genomic and the latter mitochondrial DNA replication. Based on the current genetic data, both RECQL p.I156M and POLG p.L392V represent novel breast cancer predisposing alleles.
For more information: https://www.ncbi.nlm.nih.gov/pubmed/29341116
Last updated: 10.8.2018