{"id":26937,"date":"2021-03-24T11:00:00","date_gmt":"2021-03-24T11:00:00","guid":{"rendered":"http:\/\/56b82d79f3503143c719538ecc348dfc"},"modified":"2024-11-03T15:15:00","modified_gmt":"2024-11-03T15:15:00","slug":"prevalence-of-alk-alterations-in-non-small-cell-lung-cancer-determined","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/prevalence-of-alk-alterations-in-non-small-cell-lung-cancer-determined\/","title":{"rendered":"Prevalence of ALK Alterations in Non-Small Cell Lung Cancer Determined"},"content":{"rendered":"

A large comprehensive analysis of patient-specific alterations of the anaplastic lymphoma kinase (ALK<\/em>) gene occurring in non-small cell lung cancer (NSCLC) reported at the European Lung Cancer Virtual Congress 2021<\/a> (25-27 March) provided additional insight into the landscape of ALK<\/em> alterations that may guide treatment of NSCLC.<\/p>\n

Aakash Desai from the Division of Oncology, MayoClinic in Rochester, MN, USA conducted a study describing the landscape of ALK<\/em> alterations emphasising that the detection of ALK<\/em> gene rearrangements in patients with newly diagnosed NSCLC remains critical. Recently, lorlatinib was found to be potent against all known single ALK<\/em> resistance mutations including ALK G1202R<\/em> in the CROWN study1<\/sup>. ALK<\/em> alterations influence treatment decisions among the several other targeted mutations in lung cancer today.<\/p>\n

Dr. Desai and co-investigators conducted a comprehensive analysis of patient-specific ALK<\/em> alterations in NSCLC using the open-source American Association for Cancer Research (AACR) Project GENIE Cohort v8.1. Using cbioportal as a query database, they analysed 11,107 samples from 10,082 patients with lung adenocarcinoma to determine the prevalence of ALK<\/em> fusions, mutations, and copy number alterations in NSCLC.<\/p>\n

ALK<\/em> fusion upstream partners and co-alterations identified<\/h4>\n

ALK<\/em> alterations were detected in 584 (5%) of queried samples. These alterations comprised 354 (60.6%) missense mutations, 265 (45.4%) fusions, 51 (8.7%) truncating mutations, and 1 (0.17%) in-frame mutation.<\/p>\n

The investigators excluded all alterations with mutations and copy number alterations that were of unknown significance and found that 284 (2%) of samples still had significant ALK<\/em> alterations; of these 259 fusions and 25 missenses mutations were identified.<\/p>\n

Regarding the 25 missense mutations, just 7 of 284 (2.46%) were mutations with G1202R protein change, 7 of 284 (2.46%) mutations with L1196M, and 4 of 284 with I1171N were identified; however, all of these were identified as oncogenic.<\/p>\n

The most common ALK<\/em> gene upstream partners of identified ALK<\/em> fusions were EML4<\/em> (81.5%), KIF5B<\/em> (1.5%), and SQSTM1<\/em> (1.1%). ALK<\/em> fusions were found to be significantly co-altered with HSP90AB1<\/em> mutations (p = 2.51E-04), IDH2<\/em> mutations (p = 0.027), and NRG1<\/em> mutations (p = 0.024).<\/p>\n

Conclusions<\/h4>\n

According to the authors, most ALK<\/em> variants are described as variants of unknown significance (VUS), thus limiting the impact of precision oncology.<\/p>\n

They found that ALK<\/em> fusions occur in 2.6% of lung adenocarcinomas, with EML4<\/em> being the most common upstream partner. Meanwhile, G1202R<\/em> mutations occur only among 0.07% of the ALK<\/em> alterations.<\/p>\n

The investigators also found that heat shock proteins and the Neuregulin-1 pathways may present additional opportunities for future combination targeted therapies in ALK<\/em>-positive NSCLC. <\/p>\n

No external funding was disclosed.<\/p>\n

Citation<\/h4>\n
    \n
  1. Shaw AT, Bauer TM, de Marinis F, et al.<\/em> First-Line Lorlatinib or Crizotinib in Advanced ALK<\/em>-Positive Lung Cancer. N Engl J Med<\/em> 2020;383:2018-2029. DOI: 10.1056\/NEJMoa2027187.<\/li>\n<\/ol>\n

    Reference<\/h4>\n

    21P \u2013 Desai A, Mohammed <\/sup>T, Rakshit S, et al.<\/em> The landscape of ALK alterations in non-small cell lung cancer. European Lung Cancer Virtual Congress 2021<\/a> (25-27 March).<\/p>\n

    Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"

    A large comprehensive analysis of patient-specific alterations of the anaplastic lymphoma kinase (ALK) gene occurring in non-small cell lung cancer (NSCLC) reported at the European Lung Cancer Virtual Congress 2021 (25-27 March) provided additional insight into the landscape of ALK alterations that may guide treatment of NSCLC. Aakash Desai from the Division of Oncology, MayoClinic in […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-26937","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26937","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=26937"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26937\/revisions"}],"predecessor-version":[{"id":43896,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26937\/revisions\/43896"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26937"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26937"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26937"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}