Cabrera-Becerril Augusto, Vargas-De-León Cruz, Hernández Sergio, Miramontes Pedro, Peralta Raúl
Departamento de Matemáticas, Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, México.
Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México.
PLoS One. 2017 Jul 19;12(7):e0180882. doi: 10.1371/journal.pone.0180882. eCollection 2017.
Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression. The analysis of chromosomal alterations mediated by our model reveals that multiple deleterious mutations are more frequent in precursor lesions than in CC. Cells with lethal deleterious mutations would be eliminated, which would mitigate cancer progression; on the other hand, cells with non-deleterious mutations would become dominant, which could predispose them to cancer progression. The study of somatic alterations through computer simulations of cancer progression provides a feasible pathway for insights into the transformation of cell mechanisms in humans. During cancer progression, tumors may acquire new phenotype traits, such as the ability to invade and metastasize or to become clinically important when they develop drug resistance. Non-deleterious chromosomal alterations contribute to this progression.
计算建模已被用于模拟癌症行为的异质性。宫颈癌（CC）的发展是一个细胞从非有害和有害突变中获得动态行为的过程，表现出染色体改变作为这种动态的一种表现。为了进一步确定前体病变和CC中染色体改变的进展情况，我们引入了一个计算模型来研究有害和非有害突变的动态变化，将其作为肿瘤进展的结果。我们模型介导的染色体改变分析表明，多个有害突变在前体病变中比在CC中更频繁。具有致死性有害突变的细胞将被消除，这将减轻癌症进展；另一方面，具有非有害突变的细胞将占主导地位，这可能使它们易于发生癌症进展。通过癌症进展的计算机模拟来研究体细胞改变，为深入了解人类细胞机制的转变提供了一条可行的途径。在癌症进展过程中，肿瘤可能获得新的表型特征，如侵袭和转移的能力，或者在产生耐药性时变得具有临床重要性。非有害染色体改变促成了这一进展。
