{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzp58p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzp58p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/14\\\/29\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/14\\\/29\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/14\\\/29\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/14\\\/29\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ETumor genomic profiling in clinical studies and the integration of tumor genomics into clinical practice are rapidly becoming the standard of care. This article discusses methods to apply genomics to guide clinical investigation, next-generation sequencing, how homologous recombination acts as a target and as a predictive and prognostic biomarker, and the therapeutic dissection of lung cancer.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ETumor genomic profiling in clinical studies and the integration of tumor genomics into clinical practice are rapidly becoming the standard of care.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPaul Workman, PhD, DSc, Institute of Cancer Research, London, United Kingdom, spoke about applying genomics to guide clinical investigation, noting that an improved understanding of the genetics and physiology of cancers will drive new treatments.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPriority must be given to extending the \u201cdruggable\u201d cancer genome to provide drugs for all key pathways and nodes; currently only about 5% of the cancer genome is drugged, and the remainder urgently needs to be completed [Patel MN et al. \u003Cem\u003ENat Rev Drug Discov\u003C\/em\u003E 2013]. To this end, a computational knowledge base resource for cancer translational research and drug discovery, canSAR, has been developed. It allows the integration of gene sequencing data and the prioritization of targets for drug discovery as the data emerge. Using computational techniques, targets can be validated more quickly from genome sequencing.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EA network understanding of cancer is currently lacking. Historical drug discovery has been focused on limited networks, said Prof. Workman, but druggable targets in networks outside of previous bias have been identified. His group has proposed that combinatorial targeting of different subnetworks may reduce drug resistance.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EHeat shock protein 90 (HSP90) inhibitors may turn out to be the first powerful network-based drugs, he said. HSP90 is a molecular chaperone that \u201ctalks\u201d to a large number of proteins in the cell, particularly oncogene products and mutated, amplified, and overexpressed genes. It is important for folding, function, activation, and stability of many oncogenic client proteins. It is especially important for mutant or amplified client oncoproteins and drug-resistant forms (eg, ERBB2, EGFR, ALK, BRAF, AR). HSP90 inhibitors hit multiple cancer vulnerabilities, such as targets, pathways, and hallmark traits, and thereby show tumor selectivity. They may act as the first cancer network drugs with the potential to overcome and prevent drug resistance, said Dr. Workman.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EBRAF-mutant colorectal cancers are predicted to be responsive to HSP90 inhibitors, as HSP90 inhibition has been shown to block signaling output from mutant \u003Cem\u003EBRAF\u003C\/em\u003E but not wild-type \u003Cem\u003EBRAF\u003C\/em\u003E. This blockade of signaling is related to chaperone deprivation by client proteins and HSP90 itself. Driving this depletion is \u003Cem\u003ECUL5\u003C\/em\u003E, a gene that is required for degradation of multiple kinase clients [Samant RS et al. \u003Cem\u003EProc Natl Acad Sci U S A\u003C\/em\u003E 2014], said Prof. Workman. \u003Cem\u003ECUL5\u003C\/em\u003E knockdown delays HSP90-induced signaling disruption of client proteins, indicating a key role. \u003Cem\u003ECUL5\u003C\/em\u003E could therefore be a potential biomarker of sensitivity and of a resistance mechanism.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EElaine Mardis, PhD, Washington University, St. Louis, Missouri, USA, provided the basics on next-generation sequencing and on how \u201cmassively parallel sequencing\u201d works. Massively parallel sequencing is a high-throughput deoxyribonucleic acid (DNA) sequencing technology that is capable of sequencing large numbers of different DNA sequences in a single reaction.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EAll next-generation sequencing platforms require a library obtained by either amplification or ligation with custom linkers (adapters). Each library fragment is amplified on a solid surface with covalently attached synthetic adapters that hybridize the library adapters.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EAlthough polymerase chain reaction (PCR) is an effective vehicle for amplifying DNA, in the library construction, it can introduce preferential amplification (referred to as \u201cjackpotting\u201d) of certain fragments and the need to \u201cde-duplicate\u201d identical copies (duplicate reads) that can occur. Low-input DNA amounts favor jackpotting due to lack of complexity in the library. PCR can also introduce false-positive artifacts due to substitution errors by the polymerase, which is more problematic if it occurs in early PCR cycles because the error appears as a true variant. Cluster formation is also a type of PCR, which can also introduce bias in amplifying high and low G+C content in the fragment, and as a result, coverage is reduced at these loci, potentially leading to false negatives.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EHybrid capture improves transcriptome analysis on low-input and archived samples. In hybrid capture, fragments from a whole genome library are selected by combing with probes that correspond to most human exons or gene targets. The probe DNAs are biotinylated, making selection from solution with streptavidin magnetic beads an effective means of purification.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003ENext-generation sequencing is unique in that direct step-by-step detection is performed of each nucleotide base that is being incorporated onto each amplified library fragment being sequenced. Next-generation sequencing is typically referred to as massively parallel sequencing because the stepwise process involves hundreds of thousands to hundreds of millions of reactions that are detected per instrument run.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EBecause each library fragment starts as a single piece of DNA, the amount of DNA that is contributed by that particular site in the genome and the particular ribonucleic acid in the transcriptome is measured quantitatively. The digital reads, if appropriately treated, enable direct quantitative comparisons between samples. They are typically shorter read lengths than are capillary sequencers, which deliver hundreds of nucleotides.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EChristine S. Walsh, MD, Cedars-Sinai Medical Center, Los Angeles, California, USA, reviewed how homologous recombination (HR) acts as a target and as a predictive and prognostic biomarker.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EOver the past 20 years, HR has become a target for cancer treatment, starting at the time \u003Cem\u003EBRCA1\u003C\/em\u003E and \u003Cem\u003EBRCA2\u003C\/em\u003E were isolated. HR is an error-free DNA repair pathway for double-strand DNA breaks, Dr. Walsh explained. \u003Cem\u003EBRCA1\u003C\/em\u003E and \u003Cem\u003EBRCA2\u003C\/em\u003E are genome caretaker genes that participate in the HR pathway.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EOvarian cancers can be deficient in HR either through deficiency of \u003Cem\u003EBRCA1\u003C\/em\u003E or \u003Cem\u003EBRCA2\u003C\/em\u003E through germline or somatic mutations or epigenetic \u003Cem\u003EBRCA1\u003C\/em\u003E silencing. Other HR defects may have a \u201cBRCAness\u201d phenotype in which they act like \u003Cem\u003EBRCA\u003C\/em\u003E-mutated tumors without a germline or somatic \u003Cem\u003EBRCA\u003C\/em\u003E inactivation [Cancer Genome Atlas Research Network \u003Cem\u003ENature\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003E\n         \u003Cem\u003EBRCA1\/2\u003C\/em\u003E-positive ovarian cancer patients have better survival than negative patients [Yang D et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2011; Chetrit A et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008; Cass I et al. \u003Cem\u003ECancer\u003C\/em\u003E 2003], an observation that extends to other HR-deficient cancers. HR deficiency in ovarian cancer predicts platinum sensitivity and better survival [Pennington KP et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E 2014]. \u003Cem\u003EBRCA1\/2\u003C\/em\u003E-positive breast and ovarian cancers also have an enhanced response to doxorubicin\/pegylated liposomal doxorubicin [Graeser M et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E 2010; Safra T et al. \u003Cem\u003EMol Cancer Ther\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EHR deficiency correlates with selective response to poly\u2013adenosine diphosphate ribose polymerase (PARP) inhibitors [Fong PC et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; McCabe N et al. \u003Cem\u003ECancer Res\u003C\/em\u003E 2006]. PARP is a family of enzymes involved in base excision repair, which is the key pathway in the repair of single-strand DNA breaks. BRCA-deficient cells are 1000 times more sensitive to PARP inhibition than wild-type cells [Bryant HE et al. \u003Cem\u003ENature\u003C\/em\u003E 2005; Farmer H et al. \u003Cem\u003ENature\u003C\/em\u003E 2005], and this observation led to the concept of synthetic lethality, in which a deficiency of both PARP and BRCA has a lethal effect.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EPARP inhibitors are thought to work through direct blockade of PARP enzymatic activity and PARP accumulation on DNA in a process called PARP trapping. A number of PARP inhibitors are in clinical development. Olaparib was associated with responses limited to BRCA carriers with ovarian cancer in Phase 1 study [Audeh MW et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010; Fong PC et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2010; Fong PC et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009; Tutt A et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010] and some responses in sporadic ovarian cancer in Phase 2 [Gelmon KA et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2011]. These responses correlated with platinum sensitivity. In a Phase 2 study, olaparib produced a higher overall response rate and a better toxicity profile compared with standard chemotherapy but no difference in progression-free survival in patients with \u003Cem\u003EBRCA1\u003C\/em\u003E-positive or \u003Cem\u003EBRCA2\u003C\/em\u003E-positive platinum-resistant ovarian cancer [Kaye SB et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EIn the maintenance setting in ovarian cancer, olaparib was associated with greater progression-free survival but no difference in overall survival compared with placebo, leading to an arrest in its development [Ledermann J et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012]. A post hoc analysis showed that in the BRCA carriers, however, progression-free survival was 11.2 months with olaparib versus 4.1 months with placebo (p\u0026lt;0.01) [Ledermann J et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2013], after which the manufacturer resumed development. Phase 3 trials as maintenance therapy have been launched. Other PARP inhibitors that have shown activity in advanced solid tumors are veliparib, rucaparib, and niraparib.\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003ECharles M. Rudin, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, USA, spoke on therapeutic dissection of lung cancer, which has an exceptionally high mutation burden, especially in tobacco smokers. The largest slice of the lung cancer pie is adenocarcinoma. Genomic analysis to identify at least the large slices of the lung adenocarcinoma pie is a standard of care, as driver mutations have a clear clinical significance, he said. The most frequent mutation observed is \u003Cem\u003EKRAS\u003C\/em\u003E (25%), followed by \u003Cem\u003EEGFR\u003C\/em\u003Esensitizing mutations (17%), \u003Cem\u003EALK\u003C\/em\u003E translocations (8%), \u003Cem\u003EEGFR\u003C\/em\u003E-non-sensitizing mutations (4%), and others [Kris MG et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2014]. These segments are essentially nonoverlapping, representing distinct subsets with distinct biology and distinct targetable driver alterations. No oncogenic driver is found in about one-third of lung adenocarcinomas. Survival probability is higher when lung adenocarcinoma has a driver mutation for which a targeted therapy exists compared with one for which no targeted agent exists or one that has no driver identified [Kris MG et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2014].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/14\/29\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Detection of Driver Mutations in Lung Adenocarcinoma\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2078643219\u0022 data-figure-caption=\u0022Detection of Driver Mutations in Lung Adenocarcinoma\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/14\/29\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/14\/29\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/14\/29\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14580\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-22\u0022 class=\u0022first-child\u0022\u003EDetection of Driver Mutations in Lung Adenocarcinoma\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-23\u0022\u003ESimilar analyses of squamous cell lung cancer to guide clinical trial enrollment has begun. The most commonly altered gene is \u003Cem\u003ETP53\u003C\/em\u003E, followed by \u003Cem\u003ECDKN2A, PTEN, PIK3CA\u003C\/em\u003E, and a variety of others [Cancer Genome Atlas Research Network. \u003Cem\u003ENature\u003C\/em\u003E 2012]. Relevant mutational subsets of squamous cell carcinoma are \u003Cem\u003EPTEN\u003C\/em\u003E loss (22%), \u003Cem\u003EFGFR1\u003C\/em\u003E amplification, \u003Cem\u003EPIK3CA\u003C\/em\u003E mutation, and others, with one-third having no identifiable driver alteration [Drilon A et al. \u003Cem\u003ELancet Oncol\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-24\u0022\u003EPotential drivers of small-cell lung cancer have recently been identified, with a predominance of the tumor suppressors \u003Cem\u003ETP53\u003C\/em\u003E and \u003Cem\u003ERB1\u003C\/em\u003E rather than oncogenes [Peifer M et al. \u003Cem\u003ENat Genet\u003C\/em\u003E 2012]. These data are emerging, and more work is needed to make these therapeutically intractable.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/14\/29.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzp58p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp58p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}