CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes

Takaomi Koga, Masafumi Takeshita, Kayo Ijichi, Tokujiro Yano, Yoshihiko Maehara, Katsuo Sueishi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. In this study, we analyzed abnormal checkpoint gene with forkhead-associated domain and ring finger (CHFR) methylation along with the above 3 mutations in 165 lung adenocarcinomas, evaluated the spectrum of each molecular abnormality, and correlated the results with clinical and pathologic variables. Reverse transcription-polymerase chain reaction assay, reverse transcription-polymerase chain reaction followed by direct DNA sequencing, and methylation-specific polymerase chain reaction were performed to detect these 3 mutations and CHFR hypermethylation. The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively. EGFR mutations occurred in patients who were negative for both CHFR hypermethylation and KRAS mutation. Among the 4 genetic or epigenetic abnormalities, only CHFR hypermethylation was significantly correlated with poor prognosis and lymphatic vessel invasion (P =.024). Histopathologically, the molecular abnormality that correlated with alveolar-destructive growth was the CHFR hypermethylation rather than the EGFR mutation (P =.03). Our results demonstrate that CHFR hypermethylation maybe one of the molecular abnormalities involved in a subset of lung adenocarcinomas with poor prognoses that might be induced by destructive growth and lymphatic vessel invasion of carcinoma cells. Thus, CHFR abnormality might be pursued as a novel therapeutic target against lung adenocarcinoma without an already-known mutation.

Original languageEnglish
Pages (from-to)1382-1390
Number of pages9
JournalHuman Pathology
Volume44
Issue number7
DOIs
Publication statusPublished - Jul 1 2013

Fingerprint

Methylation
Mutation
Epidermal Growth Factor Receptor
Lymphatic Vessels
Polymerase Chain Reaction
Reverse Transcription
Adenocarcinoma of lung
DNA Methylation
Growth
DNA Sequence Analysis
Oncogenes
Epigenomics
Sarcoma
Fingers
Adenocarcinoma
Carcinoma
Lung
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes. / Koga, Takaomi; Takeshita, Masafumi; Ijichi, Kayo; Yano, Tokujiro; Maehara, Yoshihiko; Sueishi, Katsuo.

In: Human Pathology, Vol. 44, No. 7, 01.07.2013, p. 1382-1390.

Research output: Contribution to journalArticle

Koga, Takaomi ; Takeshita, Masafumi ; Ijichi, Kayo ; Yano, Tokujiro ; Maehara, Yoshihiko ; Sueishi, Katsuo. / CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes. In: Human Pathology. 2013 ; Vol. 44, No. 7. pp. 1382-1390.
@article{237080ed3b3447f28549fac8bb277993,
title = "CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes",
abstract = "Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. In this study, we analyzed abnormal checkpoint gene with forkhead-associated domain and ring finger (CHFR) methylation along with the above 3 mutations in 165 lung adenocarcinomas, evaluated the spectrum of each molecular abnormality, and correlated the results with clinical and pathologic variables. Reverse transcription-polymerase chain reaction assay, reverse transcription-polymerase chain reaction followed by direct DNA sequencing, and methylation-specific polymerase chain reaction were performed to detect these 3 mutations and CHFR hypermethylation. The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7{\%}) or 16 (10{\%}) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29{\%}) or 13 (8{\%}) cases, respectively. EGFR mutations occurred in patients who were negative for both CHFR hypermethylation and KRAS mutation. Among the 4 genetic or epigenetic abnormalities, only CHFR hypermethylation was significantly correlated with poor prognosis and lymphatic vessel invasion (P =.024). Histopathologically, the molecular abnormality that correlated with alveolar-destructive growth was the CHFR hypermethylation rather than the EGFR mutation (P =.03). Our results demonstrate that CHFR hypermethylation maybe one of the molecular abnormalities involved in a subset of lung adenocarcinomas with poor prognoses that might be induced by destructive growth and lymphatic vessel invasion of carcinoma cells. Thus, CHFR abnormality might be pursued as a novel therapeutic target against lung adenocarcinoma without an already-known mutation.",
author = "Takaomi Koga and Masafumi Takeshita and Kayo Ijichi and Tokujiro Yano and Yoshihiko Maehara and Katsuo Sueishi",
year = "2013",
month = "7",
day = "1",
doi = "10.1016/j.humpath.2012.11.008",
language = "English",
volume = "44",
pages = "1382--1390",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "7",

}

TY - JOUR

T1 - CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes

AU - Koga, Takaomi

AU - Takeshita, Masafumi

AU - Ijichi, Kayo

AU - Yano, Tokujiro

AU - Maehara, Yoshihiko

AU - Sueishi, Katsuo

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. In this study, we analyzed abnormal checkpoint gene with forkhead-associated domain and ring finger (CHFR) methylation along with the above 3 mutations in 165 lung adenocarcinomas, evaluated the spectrum of each molecular abnormality, and correlated the results with clinical and pathologic variables. Reverse transcription-polymerase chain reaction assay, reverse transcription-polymerase chain reaction followed by direct DNA sequencing, and methylation-specific polymerase chain reaction were performed to detect these 3 mutations and CHFR hypermethylation. The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively. EGFR mutations occurred in patients who were negative for both CHFR hypermethylation and KRAS mutation. Among the 4 genetic or epigenetic abnormalities, only CHFR hypermethylation was significantly correlated with poor prognosis and lymphatic vessel invasion (P =.024). Histopathologically, the molecular abnormality that correlated with alveolar-destructive growth was the CHFR hypermethylation rather than the EGFR mutation (P =.03). Our results demonstrate that CHFR hypermethylation maybe one of the molecular abnormalities involved in a subset of lung adenocarcinomas with poor prognoses that might be induced by destructive growth and lymphatic vessel invasion of carcinoma cells. Thus, CHFR abnormality might be pursued as a novel therapeutic target against lung adenocarcinoma without an already-known mutation.

AB - Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. In this study, we analyzed abnormal checkpoint gene with forkhead-associated domain and ring finger (CHFR) methylation along with the above 3 mutations in 165 lung adenocarcinomas, evaluated the spectrum of each molecular abnormality, and correlated the results with clinical and pathologic variables. Reverse transcription-polymerase chain reaction assay, reverse transcription-polymerase chain reaction followed by direct DNA sequencing, and methylation-specific polymerase chain reaction were performed to detect these 3 mutations and CHFR hypermethylation. The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively. EGFR mutations occurred in patients who were negative for both CHFR hypermethylation and KRAS mutation. Among the 4 genetic or epigenetic abnormalities, only CHFR hypermethylation was significantly correlated with poor prognosis and lymphatic vessel invasion (P =.024). Histopathologically, the molecular abnormality that correlated with alveolar-destructive growth was the CHFR hypermethylation rather than the EGFR mutation (P =.03). Our results demonstrate that CHFR hypermethylation maybe one of the molecular abnormalities involved in a subset of lung adenocarcinomas with poor prognoses that might be induced by destructive growth and lymphatic vessel invasion of carcinoma cells. Thus, CHFR abnormality might be pursued as a novel therapeutic target against lung adenocarcinoma without an already-known mutation.

UR - http://www.scopus.com/inward/record.url?scp=84879215302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879215302&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2012.11.008

DO - 10.1016/j.humpath.2012.11.008

M3 - Article

VL - 44

SP - 1382

EP - 1390

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 7

ER -