MA1807 Identification of Neuroendocrine Transformation in Anaplastic Lymphoma Kinase Rearranged (ALK+) Tumors After Tyrosine Kinase Inhibitors

We describe results of a program utilizing routine biopsy post-progression in ALK+ patients for clinical and research purposes.Since 2014, ALK+ lung cancer patients treated at the Princess Margaret Cancer Centre have undergone routine biopsies at disease progression time points upon failure of an ALK-tyrosine kinase inhibitor (TKI) for both clinical purposes and research purposes, in particular to obtain tissue for primary derived xenograft (PDX) engraftment. The study found that routine combined clinical and research biopsy of ALK+ patients at time of TKI failure helped to identify these recent cases of neuroendocrine transformation as a possible mode of resistance and provide tissue for model development. This is the first time that ALK+ transformation to large cell neuroendocrine carcinoma is reported in the literature. (PP, AFF, SNMF, LN contributed equally). READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.651

Authors: P. Pal, A. Fares, D. Patel, E. Stewart, N. Perera-Low, A. Grindley, F. Allison, N. Pham, R. Shi, N. Leighl, F. Shepherd, P. Bradbury, A. Sacher, P. Rogalla, K. Yasufuku, M. Cabanero, M. Tsao, G. Liu, S. Martins-Filho, L. Nguyen

Case StudyKirk SmithOctober 1, 2019Neuroendocrine transformation, Anaplastic lymphoma kinase

P114-43 A Novel Patient Derived Synchronous Cell Pair with Different Mutations in an ALK-Rearranged Lung Adenocarcinoma Underlines Tumor Heterogeneity

ALK targeted therapy can provide prolonged clinical response rates in ALK-rearranged lung adenocarcinoma (ADC) patients. However, most tumors relapse within a few years of treatment pressure due to a variety of resistance mechanisms, including intratumoral heterogeneity. Understanding these mechanisms is of utmost importance to more precisely tailor future targeted therapies.This study is the first evidence of the synchronous establishment of two highly distinct patient-derived ALK translocated lung ADC cell lines carrying different resistant mutations. This concept supports the paramount significance of spatiotemporal intratumoral heterogeneity under targeted therapy. Furthermore, our findings showed that HDAC inhibition could enhance sensitivity of resistant tumor cells to ALK targeted therapy in vitro. Altogether, our findings provide strong evidence for the synchronous emergence of multiple resistance mechanisms and emphasize the importance of multiple site re-biopsies to better identify acquired resistance mechanisms under targeted therapy. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1194

Authors: P. Stockhammer, C.S.L. Ho, A. Bankfalvi T. Plönes, L. Hegedus, M. Schuler, C. Aigner, A. Schramm, B. Hegedus

EP101-26 Non-Small Cellular Pulmon Cancer ALK Positive in Pediatrics

This case report is from a 14-year-old adolescent patient treated in our institution with an ALK inhibitor. ALK disease is 3% to 5% of all non-cell lung cancers small adenocarcinoma type, more frequent in young people, women, nonsmokers, and with advanced disease.Male patient 14 years with respiratory symptoms productive cough. Tomography computed tomography: injury to the middle lobe and right lower lobe, biopsy: Adenocarcinoma poorly differentiated, immunohistochemistry: positive for cytokeratin 7, napsin-a, MUC-1, CK1E1 / AE3 positive and transcription factor -1 (TTF-1) and cytokeratin 20 negative, EGFR-KRAS wild type, ALK (EML-4 with clone D5F3) positive. Treatment was started with Crizotinib 250mg every 12 hours, obtaining partial response and with PFS of 36 months, gastrointestinal toxicity, hematological I grade.We report the experience of a case with excellent tolerability to an inhibitor of ALK, and its clinical benefit, (partial response and stable disease). Patients under 18..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1985

Authors: L. Ramirez, A. Guerrero Villota, J. Herrera Parga. M. Velasco, J. Lòpez

Case StudyKirk SmithOctober 1, 2019ALK, pediatric, gastrointestinal, toxicity, tolerability, Colombia

The Impact of Clinical Factors, ALK Fusion Variants, and BIM Polymorphism on Crizotinib-Treated Advanced EML4–ALK Rearranged Non-small Cell Lung Cancer

Patients' clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC). However, the results were still controversial. We analyzed outcome of 54 patients with known ALK fusion variants who received crizotinib for advanced NSCLC. Thirty of them had successful BIM polymorphism analysis and 6 (20%) had a BIM deletion. Multivariate Cox regression analysis found that previous anticancer therapy [adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI), 1.04–1.76 for each additional line of therapy, p = 0.025] and Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (aHR 8.35, 95% CI, 1.52–45.94, p = 0.015) were independent factors for progression-free survival (PFS). Only ECOG performance status ≥2 (aHR 7.20, 95% CI, 1.27–40.79, p = 0.026) was an independent factor for overall survival (..... READ ARTICLE

Frontiers in Oncology DOI:10.3389/fonc.2019.00880

Authors: Yen-Ting Lin, Yi-Nan Liu, Jin-Yuan Shih

Case StudyKirk SmithSeptember 23, 2019Non-small cell lung cancer, ALK, ALK variant, BIM, crizotinib

Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatm..... READ ARTICLE

Molecular Oncology DOI:10.1002/1878-0261.12574

Authors: Sergio Villatoro, Clara Mayo-de-las-Casas, Núria Jordana-Ariza, Santiago Viteri-Ramírez, Mónica Garzón-Ibañez, Irene Moya-Horno, Beatriz García-Peláez, María González-Cao, Umberto Malapelle, Ariadna Balada-Bel, Alejandro Martínez-Bueno, Raquel Campos, Noemí Reguart, Margarita Majem, Remei Blanco, Ana Blasco, María J. Catalán, Xavier González, Giancarlo Troncone, Niki Karachaliou, Rafael Rosell, Miguel A. Molina-Vila

Serial liquid biopsies for detection of treatment failure and profiling of resistance mechanisms in KLC1–ALK-rearranged lung cancer

Genetic rearrangements involving the anaplastic lymphoma kinase (ALK) gene confer sensitivity to ALK tyrosine kinase inhibitors (TKIs) and superior outcome in non-small-cell lung cancer (NSCLC). However, clinical courses vary widely, and recent studies suggest that molecular profiling of ALK+ NSCLC can provide additional predictors of therapy response that could assist further individualization of patient management. In summary, our findings illustrate the utility of noninvasive longitudinal molecular profiling for assessing remission status, exploring mechanisms of treatment failure, predicting subsequent clinical course, and dissecting dynamics of drug-resistant clones in ALK+ lung cancer. READ ARTICLE

Cold Spring Harbor Molecular Case Studies DOI:10.1101/mcs.a004630

Authors: Steffen Dietz, Petros Christopoulos, Lisa Gu, Anna-Lena Volckmar, Volker Endris, Zhao Yuan, Simon J. Ogrodnik, Tomasz Zemojtel, Claus-Peter Heussel, Marc A. Schneider, Michael Meister, Thomas Muley, Martin Reck, Matthias Schlesner, Michael Thomas, Albrecht Stenzinger, Holger Sültmann

Case StudyKirk SmithSeptember 4, 2019Lung adenocarcinoma

Next-generation Sequencing Identified a Novel WDPCP-ALK Fusion Sensitive to Crizotinib in Lung Adenocarcinoma

Anaplastic lymphoma kinase (ALK) fusion has been identified in 3% to 7% of patients with non–small-cell lung cancer (NSCLC), and such patients benefit greatly from ALK tyrosine kinase inhibitors (ALK-TKIs). The most common ALK fusion is echinoderm microtubule-associated protein-like 4 (EML4)-ALK, and several variants that are generally sensitive to crizotinib exist.1 In recent years, other fusion types sensitive to crizotinib, such as DYSF&ITGAV-ALK, BCL11A-ALK, and BIRC6-ALK, have been discovered by next-generation sequencing (NGS).2, 3, 4, 5, 6 However, a WD (Trp-Asp) planar cell polarity (PCP) effector gene (WDPCP)-ALK fusion has not been previously published. Here, we report this novel WDPCP-ALK fusion, which is sensitive to crizotinib, in a patient with lung adenocarcinoma. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.06.001

Authors: Zhen He, Xuan Wu, Shuxiang Ma, Cuicui Zhang, Zhe Zhang, Shuai Wang, Sheng Yu, Qiming Wang

Case StudyKirk SmithSeptember 1, 2019C1156Y, Crizotinib, Next-generation sequencing, Sensitivity, WDPCP-ALK

Response to Crizotinib Re-administration After Progression on Lorlatinib in a Patient With ALK-rearranged Non–small-cell Lung Cancer

Introduction: Chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene are detected in approximately 5% of non–small-cell lung cancers (NSCLCs) and function as oncogenic driver genes.1 First- and second-generation ALK-tyrosine kinase inhibitors (TKIs) were developed and showed clinical response for ALK-rearranged NSCLC.2, 3, 4 However, resistance to those ALK-TKIs almost develops, resulting in clinical relapse.5, 6 Lorlatinib is a third-generation ALK-TKI and has demonstrated significant antitumor activity against ALK-rearranged NSCLC with previous ALK-TKI resistance.7, 8 Although lorlatinib response was observed, relapse on lorlatinib ultimately developed.9, 10, 11 Mechanisms of lorlatinib resistance were reported,9, 10, 11 but remained unknown. Moreover, post-lorlatinib treatment has not been determined. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.06.021

Authors: Jun Sakakibara-Konishi, Hidenori Kitai, Yasuyuki Ikezawa, Yutaka Hatanaka, Takaaki Sasaki, Ryohei Yoshida, Shinichi Chiba, Shingo Matsumoto, Koichi Goto, Hidenori Mizugaki, Naofumi Shinagawa

Case StudyKirk SmithSeptember 1, 2019ALK-TKI, MET, Mutation, NGS, Sequential treatment

Inflammatory myofibroblastic tumor of bone harboring an ALK gene amplification

Inflammatory myofibroblastic tumor (IMT) is a neoplastic proliferation of myofibroblastic/fibroblastic cells with a variable admixture of inflammatory cells. It primarily affects soft tissue and viscera of children and young adults. IMT occurring in bone is extremely rare. Approximately 50% of IMTs carry a clonal rearrangement of the anaplastic lymphoma kinase (ALK) gene, while other receptor tyrosine kinase gene rearrangements have been seen in a small subset of IMT. Herein, we report the first case of IMT which harbors an ALK gene amplification rather than a rearrangement thus resulting in overexpression of the protein, arising from the femur of a 24-year-old man. Our case provides a novel pathogenesis for IMT. An overview of cytogenetic abnormalities of IMT is also integrated into this report. READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2019.152535

Authors: Kai Wang, Rongjun Guo, Gene P. Siegal, Shi Wei

Clinical significance of ROS1 5’ deletions in non-small cell lung cancer

Objectives: Patients harboring rearrangements of the ROS1 gene are eligible for first-line therapy with Crizotinib, which represents the best available treatment option. Diagnostic criteria, based on break-apart fluorescence in situ hybridization, were mirrored from ALK by analogy and include tumors with 5' deletions. However, the probability of response to Crizotinib in patients with 5' deletion in ROS1 is unknown given the rarity of this condition. Conclusion: 5' ROS1 deletions detected by FISH are associated with a high chance of response to Crizotinib in NSCLC, similarly to canonical ROS1 split-apart FISH rearrangements. However, the confirmation of the ROS1 gene fusion with at least another method, such as NGS, seems beneficial in order to define the ROS1 fusion partner and to avoid possible false positive results. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2019.07.017

Authors: Elisa Capizzi, Filippo Gustavo, Dall’Olio, Elisa Gruppioni, Francesca Sperandi, Annalisa Altimari, Francesca Giunchi, Michelangelo Fiorentino, Andrea Ardizzoni

Case StudyKirk SmithSeptember 1, 2019Non-small cell lung cancer, ROS1 fusions, ROS1 deletions, FISH, NGS, Crizotinib

The clinical impact of family history of cancer in female never-smoker lung adenocarcinoma

Accumulating evidence reveals the association between the risk of never-smoker lung cancer and family history of cancer. However, the clinicogenomic effect of family history of cancer in never-smoker lung cancer remains unknown.We screened 3,241 lung cancer patients who (a) underwent curative resection at National Cancer Center (Goyang, Korea) between 2001–2014, and (b) completed a pre-designed interview about family/smoking history at the time of diagnosis and identified 604 female never smoker lung adenocarcinoma. A positive family history of cancer [categorized as pulmonary cancer (FH-PC) or non-pulmonary cancer (FH-NPC)] was defined as a self-reported history of cancer in first-degree relatives. Survival data were followed up until January 2017. Multiplexed targeted next-generation sequencing was performed for genetic profiling.The study found that the type of family history of cancer was associated with distinct clinocogenomic subtypes and prognosis of never-smoker lung adenocarcinoma. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2019.07.031

Authors: Youngjoo Lee, Jae Hyun Jeon, Sung-Ho Goh, Hanseong Roh, Ji-Young Yun, Nak-Jung Kwon, Jin Ho Choi, Hee Chul Yang, Moon Soo Kim, Jong Mog Lee, Geon Kook Lee, Ji-Youn Han

Case StudyKirk SmithJuly 31, 2019Never smoker, Non-small-cell lung cancer, Prognosis, Family history, EGFR, ALK

Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden

Introduction: The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. Conclusions: High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.07.017

Authors: Go Makimoto, Kadoaki Ohashi, Shuta Tomida, Kazuya Nishii, Takehiro Matsubara, Hiroe Kayatani, Hisao Higo, Kiichiro Ninomiya, Akiko Sato, Hiromi Watanabe, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Shinichi Toyooka, Minoru Takata, Yoshinobu Maeda, Katsuyuki Kiura

Case StudyKirk SmithJuly 30, 2019NSCLC, Alectinib, ALK G1202R, MET, Amphiregulin

Evaluation of drug-induced lung injury by ALK inhibitor: a single center retrospective analysis

Background: Although lung cancer with ALK or ROS-1 gene fusion is rare, antitumor effect by ALK inhibitor can be highly expected. However, details of drug-induced lung injury (DILI), which can be serious side effect, remain unclear. Conclusion: Elderly people and lower renal function may require caution of DILI caused by ALK inhibitor. Images findings were subjected to OP pattern. The clinical course was not probably critical. READ ARTICLE

European Respiratory Journal DOI:10.1183/13993003.congress-2019.PA4734

Authors: Ken Koshikawa, Jiro Terada, Mitsuhiro Abe, Shunichiro Iwasawa, Masashi Sakayori, Kenji Tsushima, Koichiro Tatsumi

Case StudyKirk SmithJuly 11, 2019Drug-induced lung injury, ALK inhibitor, Pneumonia

Concomitant EGFR Mutation and EML4-ALK Rearrangement in Lung Adenocarcinoma Is More Frequent in Multifocal Lesions

Background: The coexistence of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement in patients with multifocal lung adenocarcinomas (LUAC) constitutes a rare molecular subtype of lung cancer. We aimed to investigate the intertumoral heterogeneity of pathologic and genetic characteristics of multifocal LUAC with EGFR/ALK co-alterations. Conclusion: The results highlight the importance of distinguishing synchronous primary tumors from intrapulmonary metastases, and of assessing the relative abundance of EGFR mutation and ALK rearrangement in patients with multifocal adenocarcinomas with EGFR/ALK co-alterations. READ ARTICLE

Clinical Lung Cancer DOI:doi.org/10.1016/j.cllc.2019.04.008

Authors: Jun Fan, Xiaofang Dai, Zhenkao Wang, Bo Huang, Heshui Shi, Danju Luo, Jiwei Zhang, Weijing Cai, Xiu Nie, Fred R.Hirsch

Successful salvage surgery following multimodal therapy in a patient who harboured ALK-rearranged advanced lung adenocarcinoma with multiple organ metastases

The prognosis of stage IVb non-small cell lung cancer (NSCLC) patients with multiple distant metastases or involvement of different extra-thoracic sites is poor. The prognosis following salvage surgery for patients with more than five metastases has been reported as most unfavourable. The following case is of a 71-year-old man with a 9-year survival duration after being diagnosed with stage IVb ALK-rearranged lung adenocarcinoma, who was treated for 6 years with whole-brain radiotherapy, pemetrexed-based chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) including ceritinib and alectinib, and salvage sublobar resection of the primary lung cancer and who obtained treatment-free remission (TFR) for more than 3 years following surgery. READ ARTICLE

Respirology Case Reports DOI:10.1002/rcr2.451

Authors: Yoshitsugu Horio, Tetsuya Mizuno, Yukinori Sakao, Yoshitaka Inaba, Yasushi Yatabe, Toyoaki Hida"

Case StudyKirk SmithJune 24, 2019Salvage surgery, multimodal therapy, ALK, lung adenocarcinoma, metastases

Effect of bevacizumab on brain radiation necrosis in anaplastic lymphoma kinase-positive lung cancer

Central nervous system (CNS) metastases from anaplastic lymphoma kinase (ALK)-positive lung cancer often results in failure of ALK-tyrosine kinase inhibitor (TKI) therapy. Patients with uncontrolled CNS metastases receive radiation therapy, which sometimes causes brain radiation necrosis. We added bevacizumab (15 mg/kg, every 3–4 weeks) to the regimen of four ALK-positive lung cancer patients with brain radiation necrosis who were receiving ALK-TKI therapy. A decrease in brain radiation necrosis was seen in all the patients, and an improvement in symptoms was seen in three patients. In one patient who was receiving corticosteroid therapy, we could taper the dose and subsequently discontinue it. While one patient discontinued bevacizumab because of adverse events, the other three continued with the treatment. Therefore, the combination of bevacizumab with ALK-TKI seems to be an effective, manageable, and tolerable treatment for brain radiation necrosis. READ ARTICLE

Respirology Case Reports DOI:10.1002/rcr2.454

Authors: Kengo Tanigawa, Keiko Mizuno, Yusuke Kamenohara, Taiji Unoki, Shunsuke Misono, Hiromasa Inoue

Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib

Objectives: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC. Conclusions: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib. READ ARTICLE

Lung Cancer: 10.1016/j.lungcan.2019.05.025

Authors: Niamh Coleman, Andrew Wotherspoon, Nadia Yousaf, Sanjay Popat

The repertoire of genetic alterations in salivary duct carcinoma including a novel HNRNPH3-ALK rearrangement

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy with limited treatment options and poor outcome. Twenty-nine primary resected SDC, including 15 SDC de novo (SDCDN), and 14 SDC ex pleomorphic adenoma (SDCXPA) were subjected to the massive parallel sequencing assay (MSK-IMPACT) targeting 287 to 468 cancer-related genes. TP53 was the most frequently altered gene (69%). TP53 mutations and ERBB2 amplification were more frequent in SDCXPA than in SDCDN (P = .0007 and P = .01, respectively). Potentially targetable mutations were detected in 79% (23/29) of SDC involving ERBB2 (31%), PIK3CA (28%), HRAS (21%), ALK (7%) and BRAF (3%), and 22% (5/23) of those cases harbored possible primary resistance mutations involving CCNE1, NF1 and PTEN. A novel HNRNPH3-ALK rearrangement was found in one SDCDN. In another case, EML4-ALK fusion detected in the primary tumor was associated with ALK G1202R secondary resistance mutation in the post-treatment metastasis. A germline analysis of the DN..... READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2019.03.004

Authors: Snjezana Dogan, Charlotte K. Y. Ng, Bin Xu, Rahul Kumar, Lu Wang, Marcia Edelweiss, Sasinya N. Scott, Ahmet Zehir, Alexander Drilon, Luc, G. T. Morris, Nancy Y. Lee,Cristina R. Antonescu, Alan L. Ho, Nora Katabi, Michael F. Berger, Jorge S. Reis-Filho

Feasibility of liquid biopsy using plasma and platelets for detection of anaplastic lymphoma kinase rearrangements in non-small cell lung cancer

Purpose: Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. Conclusion: Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors. READ ARTICLE

Journal of Cancer Research and Clinical Oncology DOI:10.1007/s00432-019-02944-w

Authors: Cheol-Kyu Park, Ji-Eun Kim, Min-Seok Kim, Bo-Gun Kho, Ha-Young Park, Tae-Ok Kim, Hong-Joon Shin, Hyun-Joo Cho, Yoo-Duk Choi, In-Jae Oh, Young-Chul Kim

Targeting SLMAP-ALK—a novel gene fusion in lung adenocarcinoma

Assessment of ALK gene rearrangements is strongly recommended by the Molecular Testing Guideline for Selection of Lung Cancer Patients proposed by IASLC, AMP, and CAP at the time of diagnosis for patients with advanced stage disease. Non-small-cell lung cancer (NSCLC) with ALK gene rearrangements or the resulting fusion proteins have been, for the most part, successfully targeted with ALK tyrosine kinase inhibitors (TKIs). The most frequent rearrangement, the EML4-ALK oncogenic fusion, has more than 10 distinct variants, each with a discrete breakpoint in EML4. Recent studies have suggested that EML4-ALK variants may have differential responses to TKIs. Additionally, non-EML4-ALK fusions that result from ALK rearrangements with diverse 5′ partners could possibly have varied biologic and clinical implications in their therapeutic responses and outcomes of patients with NSCLC. Existing literature documents at least 20 non-EML4 fusion partners for ALK, and the clinical responsiveness to c..... READ ARTICLE

Cold Spring Harbor Molecular Case Studies DOI:10.1101/mcs.a003939

Authors: Carlos Pagan, Subit Barua, Susan J. Hsiao, Mahesh Mansukhani, Anjali Saqi, Vundavalli Murty, and Helen Fernandes

Case StudyKirk SmithJune 1, 2019Lung adenocarcinoma, SLMAP-ALK fusion