Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

Abstract

RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancers. We retrospectively collected 6125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with proportion of 1.4% in our cohort. The median age at diagnosis was 58 years and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequently fusion type and accounted for 53.8% (57/106) of all RET fusions identified, with K15-R12 as the most frequent variant (71.9%). Among 47 RET-positive patients profiled with larger panels, 72.3% (34/47) harbored concurrent alterations. TP53 ranked as the most common concurrent alteration and concomitant EGFR oncogenic alterations were identified in 7 patients. Moreover, we presented an adenocarcinoma patient harboring concurrent RET fusion and EGFR L858R responded to combinatorial treatment of cabozantinib and osimertinib, with a progression-free survival of 5 months. Our study improved knowledge of clinical characteristics and molecular features of RET-rearranged Chinese lung cancers. It might be helpful for guiding clinicians for more effective personalized diagnostic and therapeutic approaches.

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States

“…Each of these studies included less than 20 patients with RET fusion-positive disease. Several larger studies have similarly described patients with RET fusions, but no comparison group was available [ 30 , 33 – 35 ].…”

Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study

“…Nonetheless, Wang et al [39] reported that one unique mutational signature in Chinese patients with NSCLC is associated with an increasing EGFR mutation rate together with gene fusions, such as RET and ALK. In one retrospective analysis, concurrent EGFR mutations were found in 7 of 47 RET-rearranged adenocarcinomas [3]. In our study, patients with acquired RET-rearrangement after progression on EGFR TKIs were excluded due to the concern of the potential prognostic implications of frontline EGFR-TKI administration, and no co-existence of other driver-gene alteration appeared.…”

“…The dawn of the targeted therapy era saw the discovery of receptor tyrosine kinase RET fusion in 1-2% of nonsmall cell lung cancers (NSCLC) [1,2] and proved it to be tumorigenic and targetable. Regarding the tumorigenicity, although several studies reported the prevalence of concomitant genetic alterations based on a limited sample size [3][4][5][6], the effects of these concomitant alterations on clinical outcomes were scant.…”

Long non-coding RNA NORAD exhaustion represses prostate cancer progression through inhibiting TRIP13 expression via competitively binding to miR-495-3p

“…Li et al revealed that NORAD expression was elevated in pancreatic cancer tissues, and NORAD silencing impeded metastasis and epithelial-to mesenchymal-transition (EMT) of pancreatic cancer cells in vivo and in vitro [ 30 ]. Another research revealed that NORAD was upregulated in colorectal cancer tissues, and NORAD inhibition induced apoptosis and constrained invasion, migration, and proliferation of colorectal cancer cells [ 31 ]. Zhang et al stated that NORAD exhaustion constrained migration, proliferation, and accelerated apoptosis of PCa cells [ 13 ].…”