Clinical and genomic features of non‐small cell lung cancer occurring in families

Miyabe, Shingo; S, Itó; Sato, Iwao; Abe, Jiro; Tamai, Keiichi; Mochizuki, Mai; Fujimori, Haruna; Yamaguchi, Kazunori; Shindo, Norihisa; Shima, Hiroshi; Yamazaki, Tomoko; Abue, Makoto; Okada, Yoshinori; Yasuda, Jun

doi:10.1111/1759-7714.14825

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…91 [44], and the databases were prepared according to the descriptions on the ANNOVAR website (https://annovar.openbioinformatics.org/en/latest/: last visit, 4th December 2023). To further remove potential germline variants and platform-related biases [45], we generated another set of normal from three non-cancerous exome data in our cohort (#2, #6, and #10). After merging the three non-cancerous exome datasets with bcftools, we created a normal panel database using the convert2annovar command in the Annover package.…”

Section: Bioinformatics Of the Exome Sequencing: Annotationmentioning

confidence: 99%

Bile liquid biopsy is a useful modality for molecular diagnosis of cancerous tumors in pancreatic head lesions

Ando,

Ito,

Aoki

et al. 2024

Preprint

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Cell-free DNA (cfDNA) in the blood is a less-invasive tool to reveal genomic profiles in pancreatic and bile tract cancers (PC and BTC); however, its utility is limited owing to its small amount and fragmentation of DNA for integrated sequences. This study evaluated the quality of in bile juice to clarify the potential of genome profiling for precision treatment. We collected data from 13 patients with pancreatic-biliary tumors invading the bile duct and subsequently underwent surgical resection: 7 cholangiocarcinomas, 1 gallbladder carcinoma, 3 ampullary carcinomas, 1 pancreatic cancer, and 1 intraductal papillary mucinous carcinoma. Whole-exome sequencing-based extracted DNA from resected samples revealed pathogenic alterations of TP53, ABCA8, BRCA2, FGFR2, APC, SMAD4 and NRAS. Of the 13 patients, nine pairs of cfDNA from bile and plasma were analyzed. Bile contained more (and longer fragments) cfDNAs compared with plasma. The most representative alterations in TP53, KRAS, PIK3CA, BRAF and NRAS were detected in bile cfDNA. Thus, bile cfDNA indicated better quality and quantity for sequence analysis and reflected tumor-derived genetic variation. Bile cfDNA is a useful tool for liquid biopsy in genomic profiling and precision medicine.

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Section: Bioinformatics Of the Exome Sequencing: Annotationmentioning

confidence: 99%

Bile liquid biopsy is a useful modality for molecular diagnosis of cancerous tumors in pancreatic head lesions

Ando,

Ito,

Aoki

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Clinical and genomic features of non‐small cell lung cancer occurring in families

Miyabe

Sato

et al. 2023

Thoracic Cancer

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Background: Exposure to environmental carcinogens, such as through smoking, is a major factor in the carcinogenesis of non-small cell lung cancer (NSCLC). However, genetic factors may also contribute. Methods: To identify candidate tumor suppressor genes for NSCLC, we included 23 patients (10 related pairs and 3 individuals) with NSCLC who had other NSCLC-affected first-degree relatives in a local hospital. Exome analyses for both germline and somatic (NSCLC specimens) DNA were performed for 17 cases. Germline exome data of these 17 cases revealed that most of the short variants were identical to the variants in 14KJPN (a Japanese reference genome panel of more than 14 000 individuals) and only a nonsynonymous variant in the DHODH gene, p.A347T, was shared between a pair of NSCLC patients in the same family. This variant is a known pathogenic variant of the gene for Miller syndrome. Results: Somatic genetic alterations in the exome data of our samples showed frequent mutations in the EGFR and TP53 genes. Principal component analysis of the patterns of 96 types of single nucleotide variants (SNVs) suggested the existence of unique mechanisms inducing somatic SNVs in each family. Delineation of mutational signatures of the somatic SNVs with deconstructSigs for the pair of germline pathogenic DHODH variant-positive cases showed that the mutational signatures of these cases included SBS3 (homologous recombination repair defect), SBS6, 15 (DNA mismatch repair), and SBS7 (ultraviolet exposure), suggesting that disordered pyrimidine production causes increased errors in DNA repair systems in these cases. Conclusion: Our results suggest the importance of the detailed collection of data on environmental exposure along with genetic information on NSCLC patients to identify the unique combinations that cause lung tumorigenesis in a particular family.

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Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

Ito,

Ando,

Aoki

et al. 2024

Cancer Science

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Liquid biopsy (LB) is an essential tool for obtaining tumor‐derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell‐free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor‐derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

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Clinical and genomic features of non‐small cell lung cancer occurring in families

Cited by 3 publications

References 41 publications

Bile liquid biopsy is a useful modality for molecular diagnosis of cancerous tumors in pancreatic head lesions

Bile liquid biopsy is a useful modality for molecular diagnosis of cancerous tumors in pancreatic head lesions

Clinical and genomic features of non‐small cell lung cancer occurring in families

Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers

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