Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population

Hernández‐Pedro, Norma; Soca-Chafre, Giovanny; Aláez-Verson, Carmen; Carrillo‐Sánchez, Karol; Avilés‐Salas, Alejandro; Vergara, Edgar; Arrieta, Óscar

doi:10.21149/10113

Cited by 13 publications

(9 citation statements)

References 21 publications

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“…Regarding TP53, its relatively high incidence is comparable to that reported for Latin American countries ( 18 , 19 ). This incidence, as well as the high frequency of other mutations reported in this study, particularly EGFR could be associated with a particular genetic ancestry ( 20 ).…”

Section: Discussionsupporting

confidence: 58%

Genomic landscape of lung cancer in the young

et al. 2022

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BackgroundLung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients.MethodsComparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment.ResultsOverall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability.ConclusionNSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.

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Section: Discussionsupporting

confidence: 58%

Genomic landscape of lung cancer in the young

et al. 2022

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“…EGFR alterations participate in cellular metabolism through the PI3K/Akt/mTOR axis, promoting cellular glucose uptake through increased expression and translocation of GLUT1. Upper activation of the PI3K/Akt/mTOR axis promotes downregulation of thioredoxin-interacting protein, de novo pyrimidine synthesis, and a specific amino acid profile-increasing glycolytic process [ 89 , 90 ]. Similarly, the IGF pathway is a fundamental axis for metabolism and cell growth, and it carries out transcendent functions in apoptosis and cell proliferation.…”

Section: Modifications In Cell Signaling Promoted By Metforminmentioning

confidence: 99%

Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses

et al. 2022

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Metformin has been under basic and clinical study as an oncological repurposing pharmacological agent for several years, stemming from observational studies which consistently evidenced that subjects who were treated with metformin had a reduced risk for development of cancer throughout their lives, as well as improved survival outcomes when diagnosed with neoplastic diseases. As a result, several basic science studies have attempted to dissect the relationship between metformin’s metabolic mechanism of action and antineoplastic cellular signaling pathways. Evidence in this regard was compelling enough that a myriad of randomized clinical trials was planned and conducted in order to establish the effect of metformin treatment for patients with diverse neoplasms, including lung cancer. As with most novel antineoplastic agents, early results from these studies have been mostly discouraging, though a recent analysis that incorporated body mass index may provide significant information regarding which patient subgroups might derive the most benefit from the addition of metformin to their anticancer treatment. Much in line with the current pipeline for anticancer agents, it appears that the benefit of metformin may be circumscribed to a specific patient subgroup. If so, addition of metformin to antineoplastic agents could prove one of the most cost-effective interventions proposed in the context of precision oncology. Currently published reviews mostly rely on a widely questioned mechanism of action by metformin, which fails to consider the differential effects of the drug in lean vs. obese subjects. In this review, we analyze the pre-clinical and clinical information available to date regarding the use of metformin in various subtypes of lung cancer and, further, we present evidence as to the differential metabolic effects of metformin in lean and obese subjects where, paradoxically, the obese subjects have reported more benefit with the addition of metformin treatment. The novel mechanisms of action described for this biguanide may explain the different results observed in clinical trials published in the last decade. Lastly, we present novel hypothesis regarding potential biomarkers to identify who might reap benefit from this intervention, including the role of prolyl hydroxylase domain 3 (PHD3) expression to modify metabolic phenotypes in malignant diseases.

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“…Other mutations have been identified, such as in KRAS, MET and PDGFRA (20%), HNF1A (14.4%), APC (12.2%), HER2 (11.1%), and MSH6 (10%), as well as alterations of lower frequency in PIK3CA, GUSB, ALK rearrangements, KSR1, KIT, STK11, FLT3, ERBB4, VHL, NOTCH1, GNAS, FGFR3, CDH1, BRAF, ABL1 and RB1. 173 In addition, the prevalence of ALK rearranged NSCLC is estimated at 7.6% in Mexico. Although there is a country and continental variability of ALK rearrangement frequency, the overall incidence of ALK rearranged NSCLC in Latin America does not differ from the rest of the word.…”

Section: Mexicomentioning

confidence: 99%

Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

Dalurzo¹,

Avilés‐Salas²,

Soares³

et al. 2021

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The treatment of patients with advanced non-small-cell lung cancer (NSCLC) in recent years has been increasingly guided by biomarker testing. Testing has centered on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. The presence of these mutations is predictive of response to targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs) and ALK TKIs. However, there are substantial challenges for the implementation of biomarker testing, particularly in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result. In this article, we review EGFR mutations and ALK rearrangements as predictive biomarkers for NSCLC, discuss a selection of appropriate tests and review the literature with respect to the global uptake of EGFR and ALK testing. To help improve testing rates and unify procedures, we review our experiences with biomarker testing in China, South Korea, Russia, Turkey, Brazil, Argentina and Mexico, and propose a set of recommendations that pathologists from emerging countries can apply to assist with the diagnosis of NSCLC.

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Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population

Cited by 13 publications

References 21 publications

Genomic landscape of lung cancer in the young

Genomic landscape of lung cancer in the young

Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses

Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets

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