PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit)

Review on PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit), with data on DNA, on the protein encoded, and where the gene is implicated

PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide)

Review on PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide), with data on DNA, on the protein encoded, and where the gene is implicated

SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4)

Review on SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4), with data on DNA, on the protein encoded, and where the gene is implicated

"Security Model for a Central Bank in Latin America using Blockchain"

"Banking institutions in Latin America are the target of increasingly sophisticated and advanced cyber-attacks and threats, which increase every year and leave substantial economic losses, due to the high level of global interconnection and digitization of their operations. The objective of this work is to design a model to guarantee information security in a Central Bank in Latin America using Blockchain technology. Exploratory research, observation and inductive and deductive methods are used to propose Blockchain solutions in a Central Bank. The results are a model for secure transactions in Blockchain, Smart Contract functions and a data management process. It was concluded that the security model for a central bank provides high level of information management and storage of transactions in a secure and immutable way.

Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene

Germline mutations of the LKB1 gene are responsible for Peutz-Jeghers syndrome (PJS), an autosomal dominant inherited disorder bestowing an increased risk of cancer. We have recently demonstrated that LKB1 inactivating mutations are not confined to PJS, but also appear in lung adenocarcinomas of sporadic origin, including primary tumors and lung cancer cell lines. To accurately determine the frequency of inactivating LKB1 gene mutations in lung tumors we have sequenced the complete coding region of LKB1 in 21 additional lung cancer cell lines. Here we describe the mutational status of LKB1 gene in 30 lung cancer cell lines from different histopathological types, including 11 lung adenocarcinomas (LADs) and 11 small cell lung cancers (SCLCs). LKB1 gene alterations were present in six (54%) of the LAD cell lines tested but in none of the other histological types. Similar to our previous observations in primary tumors, all point mutations were of the nonsense or frameshift type, leading to an abnormal, truncated protein. Moreover, 2 cell lines (A427 and H2126) harbored large gene deletions that spanned several exons. Hence, we have identified additional lung cancer cell lines carrying inactivating mutations of the LKB1 tumor suppressor gene, further attesting to the significance of this gene in the development of LADs and providing new natural LKB1 knockouts for studies of the biological function of the LKB1 protein

Genetic and epigenetic analyses of MBD3 in colon and lung cancer

MBD3: is a member of the methyl-CpG-binding domain family and is located on chromosome 19p13.3, a region of loss of heterozygosity in colon and lung cancers. We therefore screened samples for abnormalities in MBD3. Our results indicate that MBD3 is not a major target of genetic and epigenetic alteration in these cancers.Publisher PDFPeer reviewe

A gene-alteration profile of human lung cancer cell lines

ABSTRACT: Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in nonsmall- cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer. Hum Mutat 30, 1199–1206, 2009. & 2009Wiley-Liss, Inc

Role of LKB1 in lung cancer development

Three phenotypically related genetic syndromes and their lesions (LKB1, PTEN, and TSC1/2) are identified as frequently altered in lung cancer. LKB1, a kinase inactivated in 30% of lung cancers, is discussed in this review. Loss of LKB1 regulation often coincident with KRAS activation allows for unchecked growth and the metabolic capacity to accommodate the proliferation

MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer

Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC