Sergio Cifuentes: Somatic Landscape of Oncogenic Variants Across the Main Cancer Subtypes in Latin America
Sergio Cifuentes, Cancer Research Project Manager at CENEIT Mexico, shared a post on X about a paper by Talia Wegman-Ostrosky et al. published in JCO Global Oncology:
“Somatic Landscape of Oncogenic Variants Across the Main Cancer Subtypes in Latin America: A Narrative Review.
This is an urgent, unmet need for cancer patients in LATAM.
Talia Wegman, Andrés Bonilla amazing job.”
Authors: Talia Wegman-Ostrosky, Lucia Taja-Chayeb, Zyanya Lucia Zatarain-Barrón, Carla Daniela Robles-Espinoza, Alejandro Ruíz-Patiño, et al.
KRAS mutations are among the most frequent molecular alterations in non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, with a mutation rate of 14% in Latin America and the Caribbean (LAC). Smoking is a significant factor, with 88.1% of KRAS-mutated cases in LAC occurring in current or former smokers. Brazil has the highest KRAS mutation prevalence (18%), while Colombia has the lowest (6%).
EGFR mutations, which are mutually exclusive with KRAS, occur in 22%-26% of NSCLC cases in LAC, with Peru showing the highest EGFR mutation rate (51.1%). ALK rearrangements are found in approximately 5% of cases, reaching 11% in Peru. BRAF mutations are rare, with a 1.1%-2% prevalence, except for a 5.1% rate reported in an Argentinian study.
Melanoma data in LAC show significant variation in BRAF V600E mutation prevalence, with Mexico at 50.8%, Brazil at 34%, Colombia at 17%, and Argentina at 42%. Acral melanoma (AM), a subtype common in LAC, has a lower frequency of BRAF, RAS, and NF1 mutations compared to cutaneous melanoma.
Structural variants, including chromothripsis, are more frequent in AM, contributing to its poor prognosis and limited therapeutic options. Ongoing studies in Mexico and Brazil aim to better characterize the molecular profile of AM in LAC.
Hematologic malignancies in LAC show distinct genetic profiles compared to other populations. In acute lymphoblastic leukemia (ALL), the Ph-like subtype is more prevalent, with CRLF2 alterations in 35.3% of Hispanic patients, compared to 7.1% globally. Additionally, 80.8% of cases present IKFZ1 deletions, correlating with high mortality (64%).
AML studies in LAC, including NGS analyses in Brazil and Mexico, have not identified region-specific mutations but have improved diagnostic accuracy. In diffuse large B-cell lymphoma (DLBCL), TP53, EZH2, CREBBP, NOTCH1, and KMT2D mutations are frequently reported, with EZH2 mutations acting as a protective factor for overall survival.
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