Comprehensive genomic profiling of <scp>Brazilian</scp> non‐small cell lung cancer patients (<scp>GBOT</scp> 0118/<scp>LACOG0418</scp>)

Mascarenhas, Eldsamira; Gelatti, Ana Caroline Zimmer; Araujo, Luiz H.; Baldotto, Clarissa; Mathias, Clarissa; Zukin, Mauro; Werutsky, Gustavo; Pacheco, Patrícia; Gomes, Rafaela; Castro, Gilberto de; Lima, Vladmir Cláudio Cordeiro de

doi:10.1111/1759-7714.13777

Cited by 20 publications

(15 citation statements)

References 29 publications

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“…Additionally, 4.6% patients of the tested population were positive for ALK. This is concordant with several studies worldwide [11,15]. This makes the total driver mutation rate at 17.2% (22/128).…”

Section: Discussionsupporting

confidence: 92%

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

Ismail

Kassem

Ali

et al. 2023

J Egypt Natl Canc Inst

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Background Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC. Patients and methods This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected. Results The median age of the patients was 57 years (range: 32–79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001). Conclusion Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.

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Section: Discussionsupporting

confidence: 92%

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

Ismail

Kassem

Ali

et al. 2023

J Egypt Natl Canc Inst

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“…A recently published study found an association with somatic mutations in EGFR and ERBB2 , as well as low TMB in the tumor lung samples carrying the TP53 p.R337H variant. 47 Two of eight lung tumor samples, from the present study, had TMB information, and both cases showed a low TMB (< 10 mutations/Mb). Only one case showed ERBB2 somatic mutation, and it was not associated with the presence of EGFR mutation.…”

Section: Discussionmentioning

confidence: 57%

“… 45 Lung cancer represented 29% (220 of 755) of our samples, and 3.6% (8 of 220) of the tumor lung samples carried the TP53 p.R337H variant. Mascarenhas et al 47 analyzed 513 non–small-cell lung cancer tumor genomic profiles from a Brazilian lung cancer cohort and found the TP53 p.R337H variant in the 4.3% of the samples.…”

Section: Discussionmentioning

confidence: 99%

Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome

Sandoval

Masotti

Macedo

et al. 2021

JCO Global Oncology

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PURPOSE Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer. MATERIALS AND METHODS We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil. RESULTS The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria. CONCLUSION The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.

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“…Worldwide, the frequency of TP53 mutations in lung adenocarcinoma tumors ranges from 29% to 60%, possibly due to variations in methodology, histological subtypes, and ethnic populations [1,11,18,[20][21][22][23][24][25][26][27][28][29]. In 2014, the TCGA reported that about 45% of lung adenocarcinoma patients harbor TP53 mutations [1].…”

Section: Discussionmentioning

confidence: 99%

Disruptive and Truncating TP53 Mutations Are Associated with African-Ancestry and Worse Prognosis in Brazilian Patients with Lung Adenocarcinoma

et al. 2023

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INTRODUCTION: TP53 is the most frequently mutated gene in lung tumors, but its prognostic role in admixed populations, such as Brazilians, remains unclear. In this study, we aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in non-small cell lung cancer (NSCLC) patients in Brazil. METHODS: We analyzed 446 NSCLC patients from Barretos Cancer Hospital. TP53 mutational status was evaluated through targeted next-generation sequencing (NGS) and the variants were biologically classified as disruptive/nondisruptive, and as truncating/non-truncating. We also assessed genetic ancestry using 46-ancestry informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. We further examined associations of TP53 mutations with patients’ clinicopathological features. RESULTS: TP53 mutations were detected in 64.3% (287/446) of NSCLC cases, with a prevalence of 60,4% (n=221/366) in lung adenocarcinomas. TP53 mutations were associated with brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. Disruptive and truncating mutations were associated with a younger age at diagnosis. Additionally, cBioportal dataset revealed that TP53 mutations were associated with younger age and Black skin color. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/non-truncating and wild-type patients. CONCLUSION: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.

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Comprehensive genomic profiling of Brazilian non‐small cell lung cancer patients (GBOT 0118/LACOG0418)

Cited by 20 publications

References 29 publications

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study

Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome

Disruptive and Truncating TP53 Mutations Are Associated with African-Ancestry and Worse Prognosis in Brazilian Patients with Lung Adenocarcinoma

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