Intratumoral distribution of EGFR mutations and copy number in metastatic lung cancer, what impact on the initial molecular diagnosis?

Lupo, Audrey; Zouiti, Fouzia; Alifano, Marco; Tallet, Anne; Charpentier, Marie-Christine; Ducruit, Véronique; Devez, Fabrice; Lemaitre, Fanny; Laurent‐Puig, Pierre; Damotte, Diane; Blons, Hélène

doi:10.1186/1479-5876-12-131

Cited by 22 publications

(22 citation statements)

References 46 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some other authors also identified that the identification of EGFR mutations was independent of the localizations in the primary tumour and concordant with metastasis [80]. However, we did find some cases where the mutations were not present in all the patterns [47].…”

Section: Doi: 101159/000487440supporting

confidence: 77%

“…As the concordance rate varies between 68 and 97.1% for EGFR mutation status, we could argue that according to our group reports for most cases biopsy tissue will be representative, but not in some other cases [75,76,[79][80][81][82][83]96]. On the other end, Zhong et al [79] and Yatabe et al [84] [80] also showed that EGFR mutations are independent of the primary tumour localization, of the type of sample, and consistent between primary and metastasis, validating the use of biopsies. Intra-tumour genetic heterogeneity for EGFR or ALK could also explain different TKI response rates between patients.…”

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 75%

“…Bai et al [76] identified an ITH rate of 28.2% (24/85%); Mansuet-Lupo et al [80] identified an ITH rate of 5% (2/40); Kim et al [81] an ITH rate of 2.9% (1/34); Tomonaga et al [75] an ITH rate of 23.7% (9/38); Taniguchi et al [82] an ITH rate of 28.6% (6/21); Zhang et al [83] an ITH rate of 100% (7/7); Zhong et al [79] found an ITH rate of 15.4% (10/65), mainly in adenocarcinomas and in some studies in squamous cell carcinomas and adenosquamous carcinomas. On the other end, other studies and authors did not find ITH [29,[84][85][86].…”

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 99%

See 2 more Smart Citations

Heterogeneity in Lung Cancer

2018

View full text Add to dashboard Cite

Lung cancer diagnosis is a challenge since it is also one of the most frequently diagnosed cancers. Diagnostic challenges are deeply related to the development of personalized therapy and molecular and precise histological characterizations of lung cancer. When addressing these features, it is very important to acknowledge the issue of tumour heterogeneity, as it imposes several questions. First of all, lung cancer is a very heterogeneous disease, at a cellular and histological level. Cellular and histological heterogeneity are addressed with emphasis on the diagnosis, pre-neoplastic lesions, and cell origin, trying to contribute to a better knowledge of carcinogenesis. Molecular intra-tumour and inter-tumour heterogeneity are also addressed as temporal heterogeneity. Lung cancer heterogeneity has implications in pathogenesis understanding, diagnosis, selection of tissue for molecular diagnosis, as well as therapeutic decision. The understanding of tumour heterogeneity is crucial and we must be aware of the implications and future developments regarding this field.

show abstract

Section: Doi: 101159/000487440supporting

confidence: 77%

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 75%

Section: Molecular and Genetic Heterogeneitymentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity in Lung Cancer

2018

View full text Add to dashboard Cite

show abstract

“…EGFR gene amplification is the most developed method in the clinic to predict EGFR-TKIs treatment responses (31,32). EGFR gene amplification is also used to identify the cause of acquired resistance to EGFR-TKIs by repeated, real-time biopsy (33,34). However, the difficulty of obtaining tissue samples and the presence of critical laboratory requirements limited the application of EGFR-TKI (13,14,30).…”

Section: Discussionmentioning

confidence: 99%

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Tang

Wang

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. IntroductionLung cancer remains a common cause of mortalities worldwide, accounting for 1.6 million mortalities in 2012 and ~20% of all cancer mortalities (1). Non-small cell lung cancer (NSCLC) is the predominant type of the disease with ~80% of cases (1). In the last decade, the important discovery of mutations in the epidermal growth factor receptor (EGFR) gene had led to the development of targeted therapy and personalized medicine (2). One class of anti-tumor drugs that target EGFR is a group of small molecule inhibitors that inhibit the tyrosine kinase domain of EGFR, EGFR-tyrosine kinase inhibitors (TKIs). Examples of EGFR-TKIs include gefitinib and erlotinib (3,4).EGFR-TKIs have demonstrated initial success in some patients with activating mutations (5). However, numerous patients do not respond to the drug (6-8). Therefore, the identification of biomarkers that are predicative of response to the drug became a key issue for doctors to select the optimal therapy. To date, mutations in the EGFR gene (exon 19 deletion, exon 18 G719X and exon 21 L858R) have been reported to be predictors ...

show abstract

“…For economic consideration in clinical practice, the present study evaluated the molecular detection of EGFR and BRAF mutations using CastPCR in 144 lung adenocarcinoma samples. Although previous studies have performed EGFR mutation detection in NSCLC using CastPCR, the number of patients was relatively small, with no more than 30 samples included (22,30,41). Therefore, the present study collected samples from 144 patients with lung adenocarcinoma in order to verify its sensitivity and feasibility in larger clinical samples.…”

Section: Discussionmentioning

confidence: 99%

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

Abstract. Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important. However, the methods of molecular detection presently applied in clinical practice, particularly detection of BRAF in NSCLC patients, require further investigation. Therefore, more sensitive and economic methods are required. The present study applied the competitive allele-specific TaqMan polymerase chain reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive patients with lung adenocarcinoma, and analyzed the association between the mutation rates and patients' clinicopathological features. 51.4% (74/144) cases were identified harboring EGFR mutations. A total of 40.3% (58/144) patients carried sensitizing mutations (exon 19 deletion or L858R) and 14.6% (21/144) carried T790M mutations. 6.9% (10/144) mutation-positive patients were double-mutated. Total EGFR mutation rate was significantly increased in female compared with that of males (60.9 vs. 43.8%, P<0.05), in non-smokers compared with that of smokers (62.8 vs. 34.5%, P<0.05). In total, 8.3% (12/144) patients were identified with BRAF mutations. 16.7% were V600E (2/12) and 83.3% (10/12) were non-V600E mutants. Among the 10 non-V600E mutations, D594G accounted for 90.0% (9/10) and G469A accounted for 10.0% (1/10). Statistical analysis demonstrated that the BRAF mutation rate was not associated with any of the following clinicopathological features: Sex, age, smoking history, clinical stages, distant metastasis, differentiation degree, tumor size and regional lymph node metastasis (P≥0.05). CastPCR technology is a robust method with high sensitivity for the molecular detection of EGFR and BRAF mutations in clinical formalin-fixed paraffin-embedded samples.

show abstract

Intratumoral distribution of EGFR mutations and copy number in metastatic lung cancer, what impact on the initial molecular diagnosis?

Cited by 22 publications

References 46 publications

Heterogeneity in Lung Cancer

Heterogeneity in Lung Cancer

Serum peptide expression and treatment responses in patients with advanced non‑small‑cell lung cancer

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

Contact Info

Product

Resources

About