Genomic Profiles Specific to Patient Ethnicity in Lung Adenocarcinoma

Broët, Philippe; Dalmasso, Cyril; Tan, Eng Huat; Alifano, Marco; Zhang, Shenli; Wu, Jeanie; Lee, Ming Hui; Régnard, Jean-François; Lim, Diane S. W.; Koong, Heng Nung; Agasthian, Thirugnanam; Miller, Lance D.; Lim, Elaine; Camilleri-Broët, Sophie; Tan, Patrick

doi:10.1158/1078-0432.ccr-10-2185

Cited by 67 publications

(82 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported that the frequencies of the aberrant methylation of CpG islands in certain tumor-suppressor genes, such as MGMT and GSTP1, were different between non-Asian populations (American and Australian cases) and Asian populations (Japanese and Taiwanese cases) (23). A recent study that evaluated CNGs in lung adenocarcinomas using a common high-resolution single nucleotide polymorphism microarray, also reported that discrete differences in copy number aberrations was present between East-Asian and Western European individuals (chromosome 16p CNGs in East-Asian individuals, and chromosome 19p losses in Western European individuals) (24). Oncogenes can be activated by mutations, CNGs and/or translocations (11).…”

Section: Discussionmentioning

confidence: 99%

Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma

et al. 2015

View full text Add to dashboard Cite

Abstract. Mutations or copy number gains (CNGs) of the EGFR and KRAS genes are representative alterations in lung adenocarcinomas that are individually associated with patient characteristics such as ethnicity, smoking status and gender. However, the effects of combinations of these genetic alterations have not been statistically examined. The present study analyzed previously examined lung adenocarcinoma cases in Asian (n=166) and non-Asian (n=136) individuals in whom all four EGFR and KRAS alterations had been studied. The polynomial logistic regression models were used following adjustment for gender and smoking status, and using patients without any type of EGFR/KRAS alterations as a reference. Between the two ethnic groups, EGFR CNGs (gEGFR) occurred more frequently than EGFR mutations (mEGFR) (46 vs. 38% in Asians; 21 vs. 10% in non-Asians), whereas KRAS mutations (mKRAS) were more frequent than KRAS CNGs (gKRAS) (13 vs. 7% and 35 vs. 4%, respectively). Additionally, gEGFR and gKRAS occurred significantly more frequently in respective mutant cases, and all EGFR alterations were almost exclusive of all KRAS alterations. The polynomial logistic regression models confirmed that all types of EGFR alterations were significantly more frequent among Asian individuals than among non-Asian individuals, independent of gender and smoking status (odds ratios, 2.36-6.67). KRAS alterations occurred less frequently among Asian individuals than among non-Asian individuals, although a significant difference was not detected. The present study results indicated that the EGFR and KRAS profiles, including mutations and CNGs, differ between Asian and non-Asian individuals with lung adenocarcinoma, suggesting that ethnicity strongly affects the molecular characteristics of lung adenocarcinoma. IntroductionActivating mutations of EGFR and KRAS genes are characteristic mutations, or so-called 'driver mutations', of lung adenocarcinomas (1-3). Approximately 80% of patients with EGFR mutations (mEGFR) respond efficiently to treatment with EGFR-tyrosine kinase inhibitors (TKIs) (1,2), but KRAS mutations (mKRAS) are considered to predict resistance to EGFR-TKI therapy (4). Over the past decade, other 'driver mutations' in ALK (5), HER2 (6), and BRAF (7) have been found in lung adenocarcinomas, although mEGFR and mKRAS remain the most frequent 'driver mutations' in lung adenocarcinomas (8). Significantly, mEGFR and mKRAS are mutually exclusive and exhibit a characteristic association with clinical factors, particularly ethnicity; mEGFR are frequently observed in Asian individuals, women and never-smokers, but mKRAS are frequently observed in Caucasian individuals, men and smokers (9,10).A copy number gain (CNG) is another mechanism of oncogenic activation (11). A large-scale project to characterize copy number alterations in primary lung adenocarcinomas confirmed that EGFR and KRAS loci were significantly recurrent events when using a high-resolution genome-wide

show abstract

Section: Discussionmentioning

confidence: 99%

Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The highest frequency of MET mutations was also found in East Asians. 14,15 In light of these observations, we hypothesized that a Chinese population might present different mutations of the c-kit oncogene in terms of incidence, mutational sites or functional consequence. In our present work, we expanded the mutational analysis of the c-kit oncogene to exons 9, 11, 13, and 17 in Chinese patients with SCLC.…”

Section: Discussionmentioning

confidence: 99%

Detection of c‐kit mutational status in small‐cell lung cancer in a Chinese cohort

Cheng

et al. 2014

Thoracic Cancer

View full text Add to dashboard Cite

Background: Overexpression of KIT (CD117), a tyrosine kinase receptor, and its natural ligand, stem cell factor, are found in small-cell lung cancer (SCLC). Somatic mutations of the proto-oncogene c-kit constitutively activate KIT expression in a ligand-independent way.To explore the clinical value of the c-kit mutation as a potential target for therapy with tyrosine kinase inhibitors, the c-kit mutational status and KIT expression in tumors from Chinese patients with SCLC were analyzed. Methods: Using 107 paraffin-embedded SCLC tumor specimens, c-kit exons 9, 11, 13, and 17 were analyzed for mutations by polymerase chain reaction and direct sequencing. Results: There were no activating mutations in exons 9, 11, 13, or 17. However, a point mutation in intron 16 (81240 G>A) was found in 11 out of the 107 samples (10.3%), of which the majority were limited-stage SCLC (10/11, 90.9%). Immunohistochemical staining of tumors harboring the c-kit point mutation using the anti-CD117 antibody showed that the mutation status was not associated with the expression of KIT. Conclusion: These findings indicate that the incidence and the types of c-kit mutations in SCLC tumors found in Chinese are different from those of the Caucasian population. Nevertheless, c-kit mutations are similarly rare in both groups, implying that they may not be suitable targets for c-kit-based tyrosine kinase inhibitors.

show abstract

“…Traditionally, all KRAS mutations were thought to be associated with smoking, however a recent study failed to uphold this relationship, instead a specific type of KRAS mutation was identified that may be influenced by patient smoking status [96,97]. KRAS mutations are more common in western Europeans than in African Americans and Asians [98,99].…”

Section: Krasmentioning

confidence: 99%

Update on NSCLC tissue acquisition, processing, and profiling in the molecular age

Conterato¹,

Belanger²,

Yarmus³

et al. 2017

Hematol Med Oncol

View full text Add to dashboard Cite

As novel therapies for specific genetic mutations, chromosomal rearrangement profiles and check point inhibition in patients with NSCLC becomes more ubiquitous, adequate tissue acquisition and specimen processing has become crucial. Historically, tissue was obtained via invasive surgical resection or sampling. New tissue acquisition techniques have become increasingly commonplace in the diagnosis of NSCLC; these techniques are less invasive and at least equally reliable, if not superior, at obtaining tissue for diagnosis and molecular profiling. The preparation of tissue specimens has also been the subject of study as different methods have shown to increase cellular yield. This is of particular importance as the number of clinically significant targetable mutations and chromosomal rearrangements continues to grow, next generation sequencing becomes increasingly commonplace, and the need for more tissue increases.

show abstract

Genomic Profiles Specific to Patient Ethnicity in Lung Adenocarcinoma

Cited by 67 publications

References 33 publications

Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma

Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma

Detection of c‐kit mutational status in small‐cell lung cancer in a Chinese cohort

Update on NSCLC tissue acquisition, processing, and profiling in the molecular age

Contact Info

Product

Resources

About