A Genomics-Based Classification of Human Lung Tumors

Abstract

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

Partielles Ansprechen auf Crizotinib als Erstlinientherapie bei einem älteren männlichen Patienten mit ROS1-Translokations-positivem Bronchialkarzinom

“…Individualisierte Therapien im Sinne der personalisierten Medizin haben sich in der Behandlung von Bronchialkarzinomen als wirksam erwiesen [1]. Ein zur Aktivierung führendes Rearrangement der Rezeptortyrosinkinase ROS1 ist einer der molekularen Subtypen von Adenokarzinomen der Lunge [2], die Ansatzpunkte für eine zielgerichtete inhibierende Therapie bieten.…”

Is Liquid-Based Cytology the Magic Bullet for Performing Molecular Techniques?

“…In some pulmonary cancers, FNA is the only possible approach to obtain diagnostic material. On the other hand, lung cancers are currently classified based on genomic changes in each histological type [46,47]. As a result, appropriate management of a lung cancer patient without enough knowledge of the molecular features of the tumor is not possible and could be misleading.…”

Stratified Treatment in Lung Cancer

“…Activating EGFR mutations are detected in approximately 10 % of Caucasian NSCLC patients and the most common aberrations include the substitution L858R in exon 21 and a variety of small deletions in exon 19 [19,20,21,33,34]. With the majority of EGFR -mutant NSCLC patients being non-smokers and female, this subgroup is characterized by distinct clinico-pathological features [19,20,21,35].…”

“…Activating EGFR mutations are detected in approximately 10 % of Caucasian NSCLC patients and the most common aberrations include the substitution L858R in exon 21 and a variety of small deletions in exon 19 [19,20,21,33,34]. With the majority of EGFR -mutant NSCLC patients being non-smokers and female, this subgroup is characterized by distinct clinico-pathological features [19,20,21,35]. Superiority in terms of response rates and progression-free survival (PFS) of the first-generation TKIs gefitinib and erlotinib in first-line compared to chemotherapy was proven in several trials [10,11,12,13,15,36].…”

“…More and more molecularly stratified treatment strategies were successfully tested and implemented into clinical routine in the recent years [10,11,12,13,14,15,16,17,18]. Broad comprehensive analyses of patients' characteristics and genetic tumor profiles were undertaken by several groups in order to better understand the natural history of lung cancer and the characteristics of the different genetic subgroups [19,20,21]. Large molecular screening and treatment networks have been established in different countries to implement comprehensive genetic testing and stratified treatment into clinical routine.…”