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p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics

BACKGROUND: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could...

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Autores principales: Ruiz-Patiño, Alejandro, Rodríguez, July, Cardona, Andrés F., Ávila, Jenny, Archila, Pilar, Carranza, Hernán, Vargas, Carlos, Otero, Jorge, Arrieta, Oscar, Zatarain-Barrón, Lucia, Sotelo, Carolina, Ordoñez, Camila, García-Robledo, Juan Esteban, Rojas, Leonardo, Bermúdez, Maritza, Gámez, Tatiana, Mayorga, Diana, Corrales, Luis, Martín, Claudio, Recondo, Gonzalo, Mas, Luis, Samtani, Suraj, Ricaurte, Luisa, Malapelle, Umberto, Russo, Alessandro, Barrón, Feliciano, Santoyo, Nicolas, Rolfo, Christian, Rosell, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626684/
https://www.ncbi.nlm.nih.gov/pubmed/34823093
http://dx.doi.org/10.1016/j.tranon.2021.101276
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author Ruiz-Patiño, Alejandro
Rodríguez, July
Cardona, Andrés F.
Ávila, Jenny
Archila, Pilar
Carranza, Hernán
Vargas, Carlos
Otero, Jorge
Arrieta, Oscar
Zatarain-Barrón, Lucia
Sotelo, Carolina
Ordoñez, Camila
García-Robledo, Juan Esteban
Rojas, Leonardo
Bermúdez, Maritza
Gámez, Tatiana
Mayorga, Diana
Corrales, Luis
Martín, Claudio
Recondo, Gonzalo
Mas, Luis
Samtani, Suraj
Ricaurte, Luisa
Malapelle, Umberto
Russo, Alessandro
Barrón, Feliciano
Santoyo, Nicolas
Rolfo, Christian
Rosell, Rafael
author_facet Ruiz-Patiño, Alejandro
Rodríguez, July
Cardona, Andrés F.
Ávila, Jenny
Archila, Pilar
Carranza, Hernán
Vargas, Carlos
Otero, Jorge
Arrieta, Oscar
Zatarain-Barrón, Lucia
Sotelo, Carolina
Ordoñez, Camila
García-Robledo, Juan Esteban
Rojas, Leonardo
Bermúdez, Maritza
Gámez, Tatiana
Mayorga, Diana
Corrales, Luis
Martín, Claudio
Recondo, Gonzalo
Mas, Luis
Samtani, Suraj
Ricaurte, Luisa
Malapelle, Umberto
Russo, Alessandro
Barrón, Feliciano
Santoyo, Nicolas
Rolfo, Christian
Rosell, Rafael
author_sort Ruiz-Patiño, Alejandro
collection PubMed
description BACKGROUND: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. METHODS: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. RESULTS: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. CONCLUSIONS: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.
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spelling pubmed-86266842021-12-03 p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics Ruiz-Patiño, Alejandro Rodríguez, July Cardona, Andrés F. Ávila, Jenny Archila, Pilar Carranza, Hernán Vargas, Carlos Otero, Jorge Arrieta, Oscar Zatarain-Barrón, Lucia Sotelo, Carolina Ordoñez, Camila García-Robledo, Juan Esteban Rojas, Leonardo Bermúdez, Maritza Gámez, Tatiana Mayorga, Diana Corrales, Luis Martín, Claudio Recondo, Gonzalo Mas, Luis Samtani, Suraj Ricaurte, Luisa Malapelle, Umberto Russo, Alessandro Barrón, Feliciano Santoyo, Nicolas Rolfo, Christian Rosell, Rafael Transl Oncol Original Research BACKGROUND: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. METHODS: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. RESULTS: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. CONCLUSIONS: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR. Neoplasia Press 2021-11-22 /pmc/articles/PMC8626684/ /pubmed/34823093 http://dx.doi.org/10.1016/j.tranon.2021.101276 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Ruiz-Patiño, Alejandro
Rodríguez, July
Cardona, Andrés F.
Ávila, Jenny
Archila, Pilar
Carranza, Hernán
Vargas, Carlos
Otero, Jorge
Arrieta, Oscar
Zatarain-Barrón, Lucia
Sotelo, Carolina
Ordoñez, Camila
García-Robledo, Juan Esteban
Rojas, Leonardo
Bermúdez, Maritza
Gámez, Tatiana
Mayorga, Diana
Corrales, Luis
Martín, Claudio
Recondo, Gonzalo
Mas, Luis
Samtani, Suraj
Ricaurte, Luisa
Malapelle, Umberto
Russo, Alessandro
Barrón, Feliciano
Santoyo, Nicolas
Rolfo, Christian
Rosell, Rafael
p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title_full p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title_fullStr p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title_full_unstemmed p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title_short p.G12C KRAS mutation prevalence in non-small cell lung cancer: Contribution from interregional variability and population substructures among Hispanics
title_sort p.g12c kras mutation prevalence in non-small cell lung cancer: contribution from interregional variability and population substructures among hispanics
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626684/
https://www.ncbi.nlm.nih.gov/pubmed/34823093
http://dx.doi.org/10.1016/j.tranon.2021.101276
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