Identification and Characterization of Cancer Mutations in Japanese Lung Adenocarcinoma without Sequencing of Normal Tissue Counterparts

Abstract

We analyzed whole-exome sequencing data from 97 Japanese lung adenocarcinoma patients and identified several putative cancer-related genes and pathways. Particularly, we observed that cancer-related mutation patterns were significantly different between different ethnic groups. As previously reported, mutations in the EGFR gene were characteristic to Japanese, while those in the KRAS gene were more frequent in Caucasians. Furthermore, during the course of this analysis, we found that cancer-specific somatic mutations can be detected without sequencing normal tissue counterparts. 64% of the germline variants could be excluded using a total of 217 external Japanese exome datasets. We also show that a similar approach may be used for other three ethnic groups, although the discriminative power depends on the ethnic group. We demonstrate that the ATM gene and the PAPPA2 gene could be identified as cancer prognosis related genes. By bypassing the sequencing of normal tissue counterparts, this approach provides a useful means of not only reducing the time and cost of sequencing but also analyzing archive samples, for which normal tissue counterparts are not available.

Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

“…This is a very common issue encountered in clinical contexts; therefore, we filtered out possible germline mutations using the databases of the 1000 Genomes Project and 5000 Exomes Project to identify SMs in the absence of matched normal controls. Recently, studies using similar approaches have been reported . We expect that with increasing numbers of normal samples deposited in common databases, these methods can be further refined.…”

“…Recently, studies using similar approaches have been reported. (8,13) We expect that with increasing numbers of normal samples deposited in common databases, these methods can be further refined. Furthermore, the availability of these databases and methods allows future studies to decrease the cost of germline sequencing.…”

Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung

“…According to these reports, the prevalence of genetic alterations is 80% to 89% in TP53 and 39% to 67% in RB1 (10-12, 33). Suzuki and colleagues (34) reported that the mutation frequency of TP53 and RB1 in 97 Japanese patients with adenocarcinoma was only 23% and 1%, respectively. In contrast, the mutation frequency of RB1 (26%) in LCNEC in this study was high and similar to that revealed in a previous whole-exome sequencing study of 15 LCNECs (30%; ref.…”

Long read sequencing reveals a novel class of structural aberrations in cancers: identification and characterization of cancerous local amplifications

“…Despite the limited estimated precision and recall rates of CLCL detection using short read data at 21 % and 72 %, respectively, for all the cell lines and clinical samples taken together, we applied the constructed analytical pipeline to the whole-exome sequencing data of 514 TCGA lung adenocarcinoma (TCGA-LUAD) 3 and 97 Japanese lung adenocarcinoma (Japanese LUAD) 5 samples. We expected that the detection rate would be inherently lower, reflecting the fact that they are exome sequencing datasets.…”

“…Current information on the cancer mutations has been mostly obtained by short read sequencing. Short read sequencing data, generally consisting of tens of millions reads of up to 200-300 bases in length 12 , are the most powerful in detecting point mutations such as single nucleotide variants (SNVs) and short indels 5,13 . Significant efforts have been made to enable the identification of fusion genes by short read sequences 14 .…”