Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)

Arrieta, Óscar; Cardona, Andrés Felipe; Martín, Claudio; Mas-Lopez, Luis Alberto; Corrales-Rodriguez, Luis; Bramuglia, Guillermo F.; Castillo-Fernandez, Omar; Meyerson, Matthew; Amieva-Rivera, Eduardo; Campos‐Parra, Alma D.; Carranza, Hernán; Torre, Juan Carlos Gómez de la; Powazniak, Yanina; Aldaco-Sarvide, Fernando; Vargas, Carlos; Trigo, M.; Magallanes-Maciel, Manuel; Otero, Jorge; Sánchez-Reyes, Roberto; Cuello, M.

doi:10.1097/jto.0000000000000481

Cited by 172 publications

(155 citation statements)

References 27 publications

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“…KRAS mutations were identified in 20-30% of patients with lung cancer in North American populations (30). The prevalence of KRAS mutations in the present study was less than that observed in the Caucasian group.…”

Section: Discussioncontrasting

confidence: 51%

Targeted sequencing reveals distinct pathogenic variants in Chinese patients with lung adenocarcinoma brain metastases

Chen

Yang³

et al. 2018

Oncol Lett

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Abstract. Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform. The OncoAim™ cancer panel pipeline and OncoAim™ RNA fusion panel pipeline were used for bioinformatic analysis. Together, 43 variants were observed in 7 genes from the 28 cancer samples. The mutated genes of LCBM were tumor protein (TP)53, epidermal growth factor receptor (EGFR), catenin β1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α, mothers against decapentaplegic homolog 4, Kirsten rat sarcoma viral oncogene homolog (KRAS) and proto-oncogene B-Raf, which were exhibited in 10/15 (66.7%), 6/15 (40.0%), 3/15 (20.0%), 2/15 (13.3%), 2/15 (13.3%), 1/15 (6.7%) and 1/15 (6.7%) of samples, respectively. The mutated genes of LC were TP53, EGFR and KRAS, which were exhibited in 11/13 (84.6%), 5/13 (38.5%) and 2/13 (18.2%) of samples, respectively. echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase rearrangements were present in 1 LCBM sample. For 2 LC samples and 1 LCBM sample, no genetic alterations were observed. The NGS data also revealed a novel 4-codon deletion of TP53 (p.V166_H169del) and a novel TP53 splice site mutation (7577157-63del TACTCAG). Further potentially actionable mutations were detected in LCBM, indicating a high degree of genetic heterogeneity between the LC and LCBM samples that were analyzed. The present study demonstrated that NGS provides an improved approach for the discovery of potentially actionable mutations and the understanding of the mechanisms underlying tumor progression and evolution.

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Section: Discussioncontrasting

confidence: 51%

Targeted sequencing reveals distinct pathogenic variants in Chinese patients with lung adenocarcinoma brain metastases

Chen

Yang³

et al. 2018

Oncol Lett

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“…Interestingly, epidemiological reports have shown a higher EGFR mutation prevalence in our study population (25,26). This can be explained by different exposure factors associated such as wood smoke exposure (27), high prevalence of chronic tuberculosis infection (28) and ethnicity (29).…”

Section: Discussionmentioning

confidence: 79%

Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation

Barrón

Cardona²,

Corrales³

et al. 2018

J. Thorac. Dis.

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Background: Non-small cell lung cancer (NSCLC) harboring EGFR-sensitizing mutations has a distinct biology and heterogeneous clinical behavior. We evaluated the characteristics to progression such as clinical patterns of progression (dramatic, gradual, and local) with the prognosis of NSCLC patients treated with tyrosine kinase inhibitors (TKIs). Methods: We reviewed 123 advanced-NSCLC patients with an EGFR-sensitizing mutation treated with TKIs (gefitinib, erlotinib and afatinib). We assessed patients according to clinical factors and progression pattern to TKIs at three centers. Results: For all patients, 58.5%, 31.7% and 9.8% harbored exon19 deletion, exon21 L858R mutation and other-sensitivity mutations, respectively. Median progression-free survival (PFS) was 8.8 months (95% CI: 7.9-9.7). Sixty percent of patients were asymptomatic. Dramatic-progression was the most frequent pattern (50.4%), followed by gradual-progression (32.5%), and local-progression (17.1%). Median overall survival (OS) was 23.1 months (95% CI: 17.4-28.9). In the univariate analysis, factors associated to a longer OS included pattern [gradual-progression (32.1), dramatic (19.5) and local (18.8 months), P=0.008], and the time to progression to TKI [>12 months (38.5), 6-12 months (19.1), <6 months (9.6), P<0.001]. Multivariate analysis showed that only time to progression to TKI was independently associated to OS and PFS. Conclusions: Factors at TKI progression associated to a longer OS can define a subset of patients who may benefit from continued TKI therapy, as well as from local-ablative therapy in progression sites, especially in patients without T790M or who lack access to third-generation TKI.

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“…In lung cancer, previous reports have suggested that the incidence of specific molecular abnormalities may vary between ethnic groups and within the Latin American population [39]. Even though the explanation for this variability is not well understood, it does occur, and therefore we must identify possible factors that may explain the differences in lung cancer, such as differences in environmental hazards exposure, within the same geographic region or even within the same ethnic group [40].…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of <b><i>ALK</i></b> Rearrangements in Advanced Lung Adenocarcinoma in Latin America

Arrieta

Cardona²,

Bramuglia

et al. 2018

Oncology

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Objective: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America. Methods: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed. Results: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%). Conclusions: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.

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Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)

Abstract: Our findings support the genetic heterogeneity of NSCLC in Latin America, confirming that the frequency of EGFR mutations is intermediate between that observed in the Asian and Caucasian populations.

Cited by 172 publications

References 27 publications

Targeted sequencing reveals distinct pathogenic variants in Chinese patients with lung adenocarcinoma brain metastases

Targeted sequencing reveals distinct pathogenic variants in Chinese patients with lung adenocarcinoma brain metastases

Characteristics of progression to tyrosine kinase inhibitors predict overall survival in patients with advanced non-small cell lung cancer harboring an EGFR mutation

Molecular Epidemiology of <b><i>ALK</i></b> Rearrangements in Advanced Lung Adenocarcinoma in Latin America

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