Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

By Doron Lipson, M. Capelletti, Roman Yelensky, G. Otto, A. Parker, M. Jarosz, J. Curran, S. Balasubramanian, T. Bloom, K. Brennan and 22 more. Nature Medicine, 2012

867 citations recorded by the source corpus.

Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non–small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8–3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/517db35980f5aae43e205325c3ea44d4faf2d087

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. K. Kerr
2. Z. Du
3. M. Hellmann
4. Christine Lovly

In Pulmonary and Respiratory Medicine

1. Marc Ladanyi
2. Z. Du
3. Christine Lovly

Citations in the corpus

• Lessons from the cancer genome. (2013, neutral): “, 2012) These platforms involve testing a few hundred specific cancer-associated mutations or performing full sequencing of a limited set of cancer-associated genes (Lipson et al., 2012; Wagle et al., 2012).”
• Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology (2018, background): “Patients with RET fusion harboring tumors are usually younger than patients with an EGFR mutation and have an equal gender distribution.(67) RET fusion proteins have been detected in adenocarcinoma(37,62,64) and in adenosquamous carcinoma.”
• Mechanisms of receptor tyrosine kinase activation in cancer (2018, positive): “First, the regulatory unit of the fusion partner dictates the expression of the fusion, placing the tyrosine kinase oncoprotein under the endogenous promoter of the fusion partner [108, 126].”
• Haplotyping germline and cancer genomes using high-throughput linked-read sequencing (2016, neutral): “Exome sequencing does not detect gene fusions for which the breakpoint is more than a few hundred base pairs from an exon without custom targeting assays and extremely high sequencing coverage 22, 23 .”
• MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. (2016, neutral): “5 (59-84) 61 (30-93) 65 (42-93) Sex Male 9 (32) 30 (30) 62 (37) Female 19 (68) 69 (70) 107 (63) Smoking history, pack-years* Never-smoker 10 (36) 57 (58) 6 (4) # 10 3 (11) 10 (10) 11 (7) .”
• Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “RET fusions are found in 1%–2% of NSCLC and tend to be mutually exclusive to other lung cancer drivers [231, 232].”