Dataset Information

KMT2C expression and DNA homologous recombination repair factors in lung cancers with a high-grade fetal adenocarcinoma component.

ABSTRACT:

Background

High-grade fetal adenocarcinoma of the lung (H-FLAC) is a rare variant of pulmonary adenocarcinoma. Our previous study showed a high frequency of KMT2C mutations in lung cancers with an H-FLAC component, showing that KMT2C dysfunction may be associated with the biological features of H-FLACs.

Methods

In this study, we performed RNA sequencing and immunohistochemical analysis to identify the differentially expressed genes and corresponding pathways associated with H-FLACs, compared with common adenocarcinomas.

Results

Ingenuity pathway analysis based on RNA sequencing data revealed that DNA homologous recombination repair (HRR) pathways were significantly inactivated in H-FLAC. Expression of KMT2C, ATM, ATR, and BRCA2 was significantly lower in H-FLACs than in common adenocarcinomas, and BRCA1 expression showed a decreasing trend. Pearson correlation analyses for all cases revealed that KMT2C expression showed a strong positive correlation (R>0.7) with the expression of ATR, BRCA1, and BRCA2 genes and a moderately positive correlation with ATM expression (R=0.47). Immunohistochemical analysis showed significantly lower levels of KMT2C, ATM, ATR, and BRCA2 expression in H-FLACs than in common adenocarcinomas, and a trend of lower BRCA1 levels. Additionally, KMT2C expression showed a weak to moderate correlation with that of ATM, ATR, BRCA1, and BRCA2.

Conclusions

Cancers containing H-FLAC components showed lower levels of KMT2C and HRR factors than common lung adenocarcinomas, and their levels exhibited a positive correlation. These results support the hypothesis that loss of KMT2C function decreases the expression of the HRR factors in H-FLACs. H-FLACs with low KMT2C expression may be a good indication for poly (ADP-ribose) polymerase (PARP) inhibitor-based therapy.

SUBMITTER: Suzuki M

PROVIDER: S-EPMC10483084 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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<i>KMT2C</i> expression and DNA homologous recombination repair factors in lung cancers with a high-grade fetal adenocarcinoma component.

Suzuki Masaki M Kasajima Rika R Yokose Tomoyuki T Shimizu Eigo E Hatakeyama Seira S Yamaguchi Kiyoshi K Yokoyama Kazuaki K Katayama Kotoe K Yamaguchi Rui R Furukawa Yoichi Y Miyano Satoru S Imoto Seiya S Shinozaki-Ushiku Aya A Ushiku Tetsuo T Miyagi Yohei Y

Translational lung cancer research 20230816 8

<h4>Background</h4>High-grade fetal adenocarcinoma of the lung (H-FLAC) is a rare variant of pulmonary adenocarcinoma. Our previous study showed a high frequency of KMT2C mutations in lung cancers with an H-FLAC component, showing that KMT2C dysfunction may be associated with the biological features of H-FLACs.<h4>Methods</h4>In this study, we performed RNA sequencing and immunohistochemical analysis to identify the differentially expressed genes and corresponding pathways associated with H-FLAC ...[more]

PMID: 37691868

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