Isolated 5′ Signals Are an Atypical Pattern To Be Considered as Positive for ALK Rearrangement: A Brief Report of Three Cases and Review of the Literature

Anaplastic lymphoma kinase (ALK) rearrangement is reported in 3% to 8% of patients with lung adenocarcinoma and can be detected by fluorescent in situ hybridization (FISH) or indirectly by immunohistochemistry. In FISH assay, isolated 5′ signal (loss of 3′ signal) is usually considered negative. We report three young nonsmoking patients with stage IV lung adenocarcinoma. Strong ALK expression in tumor cells detected by immunohistochemistry was observed in all cases, but FISH revealed an isolated 5′ signal pattern. Massive parallel “next-generation” sequencing was performed in two patients and confirmed ALK rearrangement. The three patients were treated and responded to crizotinib after 14, 10, and 31 months. READ ARTICLE

Translational Oncology DOI:10.1016/j.tranon.2019.02.015

Authors: Alice Guyard, Cécile Charpy, Nathalie Théou-Anton,Anne Cremades, Frédéric Grassin, Anaïs Bourgogne, Karen Leroy, Anaïs Pujals, Christiane Copie-Bergman, Christos Chouaid, Audrey Mansuet-Lupo

Case StudyKirk SmithMay 1, 2019Isolated 5′ Signals, ALK Rearrangement

Concurrent Presence of ALK Rearrangement and MET Mutation in Lung Adenocarcinoma

During recent years, many gene mutations have been reported in lung adenocarcinoma, and target agents against driver mutations have been explored. MNNG HOS transforming gene (MET) exon 14 mutation and ALK receptor tyrosine kinase (ALK) translocation were usually mutually exclusive. However, here, we describe a case that had intratumor heterogeneity on both genetic and pathologic characteristics. Patients whose tumors harbored MET exon 14 splice site mutations or ALK rearrangement derived meaningful clinical benefit from crizotinib.4, 5 Our findings may have profound clinical implications for potential therapeutic targeting during disease progression. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2018.10.149

Authors: Tian Qiu, Fanshuang Zhang, Weihua Li, Lei Guo, Jianming Ying

Case StudyKirk SmithFebruary 1, 2019ALK Rearrangement, MET Mutation, Lung Adenocarcinoma