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Cancer-linked mutations A large-scale genetic analysis of more than 400 breast, lung, ovarian and prostate cancer samples has identified thousands of cancer-related mutations. Kan et al . analysed DNA from cancer patients and identified 2,576 somatic mutations across 1,507 coding genes. Of these, 77 are thought to be significantly mutated, implying possible pathogenic roles for protein kinases, G protein-coupled receptors and other potential therapeutic targets. These authors performed a large-scale study in which they identified 2,576 somatic mutations across 1,507 coding genes from 441 breast, lung, ovarian and prostate cancer types and subtypes. The study provides an overview of the mutational spectra across major human cancers, implies an expanded role for Gα subunits in multiple cancer types and identifies several potential therapeutic targets. The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics 1 . Here we report the identification of 2,576 somatic mutations across ∼1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes. Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8 , BAI3 , AGTRL1 (also called APLNR ) and LPHN3 , and other druggable targets. Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS , indicating an expanded role for gα subunits in multiple cancer types. Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Gα subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis. Our study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.

Lung cancer mutations Complete genome sequencing has already provided insights into the mutation spectra of a number of cancer types, including lung cancer. The latest sequencing technologies mean that it is possible to provide a genome-wide view of mutation differences, and this has now been done for lung cancer, comparing the complete sequences of a primary lung tumour — an adenocarcinoma in a male who reported smoking an average of 25 cigarettes a day for 15 years — and adjacent normal tissue. The comparison revealed more than 50,000 point mutations of which 530 were validated, 392 of them in coding regions, including previously known variations such as KRAS proto-oncogene mutation and amplification. The data suggest that genetically complex tumours may contain many partially redundant mutations, and that identifying recurrent cancer-causing driver mutations will require the sequencing of many more samples yet. Complete genome sequencing has already provided insights into the mutation spectra of several cancer types. Here, the first complete sequences are provided of a primary lung tumour and adjacent normal tissue. Comparison of the two reveals a variety of somatic mutations in the cancer genome, including changes in the KRAS proto-oncogene. The results reveal a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes, and selection against mutations in promoter regions. Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease 1 , 2 . Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum 3 , 4 , 5 , 6 , 7 , 8 . Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines 9 , 10 , 11 , 12 , 13 . Here we present the complete sequences of a primary lung tumour (60× coverage) and adjacent normal tissue (46×). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.

Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG -negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines. Conclusions Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as MSMB-NCOA4 , may play functional roles in cancer.

Sekar Seshagiri and colleagues report exome, transcriptome and copy-number alteration data in small-cell lung cancer. The authors find SOX2 amplification in 27% of samples and also identify a recurrent RFL - MYCL1 fusion. Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor prognosis. Here, we obtained exome, transcriptome and copy-number alteration data from approximately 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines. We also obtained data for 4 primary tumors and 23 SCLC cell lines. We identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein–coupled receptors and chromatin-modifying proteins. We found that several members of the SOX family of genes were mutated in SCLC. We also found SOX2 amplification in ∼27% of the samples. Suppression of SOX2 using shRNAs blocked proliferation of SOX2 -amplified SCLC lines. RNA sequencing identified multiple fusion transcripts and a recurrent RLF - MYCL1 fusion. Silencing of MYCL1 in SCLC cell lines that had the RLF-MYCL1 fusion decreased cell proliferation. These data provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention.

Loop-mediated isothermal amplification (LAMP) is an emerging nucleic acid based diag- nostic approach that is easily adaptable to the field settings with limited technical resources. This study was aimed to evaluate the LAMP assay for the detection and identification of Plasmodium falciparum and P. vivax infection in malaria suspected cases using genus and species-specific assay. The 18S rRNA-based LAMP assay was evaluated for diagnosis of genus Plasmodium, and species- specific diagnosis of P. falciparum and P. vivax, infection employing 317 malaria suspected cases, and the results were compared with those obtained by 18S nested PCR (n-PCR). All the samples were confirmed by microscopy for the presence of Plasmodium parasite. The n-PCR was positive in all Plasmodium-infected cases (n=257; P. falciparum=133; P. vivax=124) and negative in microscopy negative cases (n=58) except for two cases which were positive for P. vivax, giving a sen- sitivity of 100% (95% CI: 97.04-100%) and a specificity of 100% (95% CI: 88.45-99.5%). Genus-specific LAMP assay missed 11 (3.2%) microscopy and n-PCR confirmed vivax malaria cases. Considering PCR results as a refer- ence, LAMP was 100% sensitive and specific for P. falciparum, whereas it exhibited 95.16% sensitivity and 96.7% specificity for P. vivax. The n-PCR assay detected 10 mixed infection cases while species-specific LAMP detected five mixed infection cases of P. vivax and P. falciparum, which were not detected by microscopy. Genus-specific LAMP assay displayed low sensitivity. Falciparum specific LAMP assay displayed high sensitivity whereas vivax specific LAMP assay displayed low sensitivity. Failed detection of vivax cases otherwise confirmed by the n-PCR assay indicates exploitation of new targets and improved detection methods to attain 100% results for P. vivax detection.

World Health Organization (WHO) in 2010, recommended 0.75 mg/kg single dose primaquine for killing gametocytes after ruling out glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, considering the practical feasibility of G6PD testing, WHO revised the recommendation in 2012 to 0.25 mg/kg single dose primaquine on day-1. This study aims to investigate the efficacy and safety of single-low dose primaquine (0.25 mg/kg) administered on day-1 to intervention arm compared to standard regimen, high-dose primaquine (0.75 mg/kg) administered on day-2 to control arm. This is a hospital based, open-label, multi-centric, randomized-controlled trial being conducted at four different sites in India, with a target sample size of 496 i.e., 124 participants per site. Participants above 18 years of age with uncomplicated P. falciparum malaria and normal glucose-6-phosphate dehydrogenase (G6PD) activity, defined as > 4.0 IU/g Hb using the point-of-care test, weight > 40 kg, haemoglobin > 8 g/dL are treated with ACT and randomized to either control or intervention arm. Efficacy assessment is based on gametocytemia as inferred from examination of stained peripheral blood smears during enrolment and follow-up. In addition, quantitative nucleic acid sequence-based amplification (QT-NASBA) for Pfs25 mRNA, will be used to quantify the gametocytes on day 1, 2/3, 7, and 14. Safety assessment during 14-day follow-up will be based on percentage of participants with more than 25% drop in haemoglobin, haemoglobin drop of 5 g/dl, haemoglobin value less than 8 g/dl, mean of maximum drop in haemoglobin during 28-day follow-up; and frequency of adverse events reported during the follow-up in both the arms. The primary outcome of the study is based on gametocyte density and point prevalence of gametocyte (efficacy) and haemoglobin concentration (safety) from enrolment to day 14 (for efficacy) and day 28 (for safety). Study has been approved by Institutional Ethics Committee (NIMR/IEC-M/2023/970/v6-Jun/01). The study findings will be disseminated through publications in peer-reviewed journals as well as academic presentations. The findings will support evidence-based recommendations for national malaria control programs in India, potentially advocating for the adoption of the lower dose primaquine regimen. CTRI/2025/07/091988 (CTRI registration). Enrollment started in August, 2025. The trial is going on.

Disorder in high entropy alloys, arising from the random distribution of multiple elements, plays a crucial role in their novel properties desirable for various advanced engineering applications. We investigate the role of compositional and structural disorder on the electronic structure of osmium-based superconducting high entropy alloys, (Ru/Re)\\(_0.35\\)Os\\(_0.35\\)Mo\\(_0.10\\)W\\(_0.10\\)Zr\\(_0.10\\), using photoemission spectroscopy and density functional theory (DFT). Elemental and cumulative core level shifts are found to be commensurate with elemental electronegativities and valence electron counts (VEC), respectively. Valence band spectra together with DFT results indicate that the crystal structure plays an important role in deciding the electronic structure of these high entropy alloys. Through temperature dependent high-resolution spectra, we unveil strongly suppressed spectral density of states (SDOS) in the close vicinity of Fermi level. Energy and temperature dependence of the SDOS in accordance with Altshuler-Aronov theory confirms localization of charge carriers in the presence of strong intrinsic disorder. Computed electron-phonon coupling strength and superconducting transition temperature aligning reasonably well with experiments further shed light on phonon-mediated pairing mechanism and role of disorder in these systems. Our results provide a way forward to the understanding of superconducting high entropy alloys through strategic control of disorder, VEC and crystal structure.

Nontrivial topology in type-II Dirac semimetal NiTe\\(_2\\) leading to topologically protected surface states give rise to fascinating phenomena holding great promise for next-generation electronic and spintronic devices. Key parameters \\(-\\) such as lattice parameter, disorder, vacancies, and electron correlation \\(-\\) significantly influence the electronic structure and, subsequently, the physical properties. To resolve the discrepancy between the theoretical description and experimentally observed topological surface states, we comprehensively investigate the electronic structure of NiTe\\(_2\\) using angle-resolved photoemission spectroscopy and density functional theory. Although the bulk electronic structure is found to be well-described within mean field approaches, an accurate description of topological surface states is obtained only by incorporating surface electronic correlation. We reveal that the strongly correlated surface states forming Dirac-like conical crossing much below Fermi level have hybridized Ni 3\\(d\\) and Te 5\\(p\\) character. These findings underscore the intricate interplay between electron correlation and band topology, broadening our understanding of many-body correlation effects on the topological surface states in quantum materials.

Protein kinease C plays an important role in angiogenesis and apoptosis in cancer. During the phase of angiogenesis the growth factor is up regulated where as during apoptosis the growth factor is down regulated. For down regulation of growth factor the pH environment of intra-cellular fluid has a specific range in the alkaline medium. Protein kinease C along with E-coli through interaction of Selenometabolite is able to maintain that alkaline environment for the apoptosis of the cancer cell with inhibition of the growth factor related to antioxidant/oxidant ratio. The present paper through implementation of Artificial Neural Network and Decision Tree has focused on metastasis linked with Capacitance Relaxation phenomena and down regulation of growth factor (VGEF). In this paper a distributed neural network has been applied to a data mining problem for classification of cancer stages inorder to have proper diagnosis of patient with PKC sensor. The Network was trained off line using 270 patterns each of 6 inputs. Using the weight obtained during training, fresh patterns were tested for accuracy in diagnosis linked with the stages of cancer. [PUBLICATION ABSTRACT]