HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers

Li, Bob T.; Ross, Dara S.; Aisner, Dara L.; Chaft, Jamie E.; Hsu, Meier; Kako, Severine; Kris, Mark G.; Varella‐Garcia, Marileila; Arcila, Maria E.

doi:10.1016/j.jtho.2015.10.025

Cited by 226 publications

(213 citation statements)

References 15 publications

Supporting

Mentioning

207

Contrasting

Order By: Relevance

“…The prevalence of HER2 mutations has been reported previously to range from 1% to 6% in NSCLC [16-22]. Wang and colleagues reported 1943 NSCLC and found a HER2 mutation rate of 1.3%.…”

Section: Discussionmentioning

confidence: 99%

HER2 mutations in Chinese patients with non-small cell lung cancer

Song

Shi

et al. 2016

Oncotarget

View full text Add to dashboard Cite

BackgroundERBB2 (HER2) is a driver gene identified in non-small cell lung cancer (NSCLC). The prevalence, clinicopathology, genetic variability and treatment of HER2-positive NSCLC in Chinese population are unclear.Patients and MethodsEight hundred and fifty-nine patients with pathologically confirmed NSCLC were screened for HER2 mutations using Sanger sequencing. Next-generation sequencing (NGS) was performed in positive cases. HER2 amplification was detected with FISH. Overall survival (OS) was evaluated using Kaplan-Meier methods and compared with log-rank tests.ResultsTwenty-one cases carrying HER2 mutations were identified with a prevalence of 2.4%. HER2 mutations were more frequently encountered in females, non-smokers and adenocarcinoma. NGS was performed in 19 out of 21 patients, The results showed 16 cases with additional genetic aberrations, most commonly associated with TP53 (n = 6), followed by EGFR (n = 3), NF1 (n = 3), KRAS (n = 2) and other mutations. One patient harbored HER2 amplification. Four patients with stage IV received afatinib treatment, and three showed stable disease with a median progression-free survival of 4 months and one patient was diagnosed with progressive disease.ConclusionHER2 mutations represent a distinct subset of NSCLC. NGS showed that HER2 mutations commonly co-existed with other driver genes. Afatinib treatment displayed moderate efficacy in patients with HER2 mutations.

show abstract

“…The prevalence of HER2 mutations has been reported previously to range from 1% to 6% in NSCLC [16-22]. Wang and colleagues reported 1943 NSCLC and found a HER2 mutation rate of 1.3%.…”

Section: Discussionmentioning

confidence: 99%

HER2 mutations in Chinese patients with non-small cell lung cancer

Song

Shi

et al. 2016

Oncotarget

View full text Add to dashboard Cite

show abstract

“…HER2 mutations most commonly consist of a 12 base pair in-frame insertion YVMA (p.A775_G776insYVMA) in exon 20, leading to downstream activation of the PI3K-AKT and MEK-ERK pathways [2, 3]. This mutation is most commonly found in female patients, never smokers, and those with lung adenocarcinomas [3, 5, 6]. Patients with HER2 -mutant lung cancers were reported to have a median overall survival of 1.6–1.9 years from the time of stage IV diagnosis [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers

et al. 2016

Self Cite

View full text Add to dashboard Cite

Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46–78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2–2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0–21 months): 6.2 months for pemetrexed ± platinum/bevacizumab, 4 months for taxane ± platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3–16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care.

show abstract

“…Gene amplification and overexpression of ERBB2, FGFR2 and MAPKs have been reported in gastroesophageal cancers545556. Of note, targeting signaling kinases has been a promising therapeutic approach in several cancer types565758. In addition to these important signaling molecules, the results predicted activation of CD44 pathway, which plays an important role in the development and progression of cancer5960.…”

Section: Resultsmentioning

confidence: 99%

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Peng

Guo

Chen

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.

show abstract

HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers

Cited by 226 publications

References 15 publications

HER2 mutations in Chinese patients with non-small cell lung cancer

HER2 mutations in Chinese patients with non-small cell lung cancer

Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Contact Info

Product

Resources

About