Mutational analysis of multiple lung cancers: Discrimination between primary and metastatic lung cancers by genomic profile

Abstract

In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.

Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis

“…Finally, the number of targeted genes in our NGS panel may be relatively small. Recent studies on mutational analysis using NGS have included a larger number of targeted genes than we did . Begg et al indicated that at least 20 markers are required from a statistical perspective to distinguish between clonal and independent tumors with high accuracy .…”

“…With the advances in high‐throughput sequencing technologies, mutational analysis for specific driver and suppressor genes has been shown to be useful for distinguishing between multiple primary tumors and pulmonary metastases . In recent years, in patients with MLC, several reports have been published of mutational analyses by NGS, which allows analysis for multiple gene mutations at once . In this study, we investigated the mutational profiles by NGS of 20 lung cancer‐related genes in surgically resected paired tumors obtained from the same patients and compared the clinicopathological diagnoses with the diagnoses based on mutational evaluation.…”

“…[11][12][13] In recent years, in patients with MLC, several reports have been published of mutational analyses by NGS, which allows analysis for multiple gene mutations at once. 14,15 In this study, we investigated the mutational profiles by NGS of 20 lung cancer-related genes in surgically resected paired tumors obtained from the same patients and compared the clinicopathological diagnoses with the diagnoses based on mutational evaluation. In histopathologically IM cases, we found a good concordance rate (86%) with the diagnosis based on the mutational evaluation.…”

“…Recent studies on mutational analysis using NGS have included a larger number of targeted genes than we did. 14,15 Begg et al indicated that at least 20 markers are required from a statistical perspective to distinguish between clonal and independent tumors with high accuracy. 25 In the present study, although we analyzed 20 lung cancerrelated genes, paired tumors from five patients (cases 10, 11, 14, 23, and 31) failed to show any mutations.…”

Elucidation of radiation-resistant clones by a serial study of intratumor heterogeneity before and after stereotactic radiotherapy in lung cancer

“…The total amount of DNA used for next-generation sequencing analysis was 1.62 ng of the biopsy specimens and 3.76 ng of the surgical specimens (Table S1). An assay system that could analyze the entire exon region of the 53 lung cancerrelated genes (68,046 amino acids) was developed in house, and the samples were subjected to next-generation sequencing (5)(6)(7). This assay system was used to identify mutations in the 53 significantly mutated genes, which were identified from 408 patients with lung cancer by total exon analysis (8,9).…”