Modeling the pathway of breast cancer in the Middle East

This paper proposed an approach for the identification of mutation mechanisms of breast cancer in women in four member countries of the Middle East Cancer Consortium i.e. Egypt, Jordan, Cyprus and Israel (Arabs and Jews). We set up multistage models including both gene mutation and the clonal expansion of intermediate cells. We fit the data-set related to the incidence of female breast cancer in the four member countries. Our simulation results show that the maximum number of driver mutations of breast epithelium stem cells of Egyptian women is 13, whereas there are 14 driver mutations in the genome of stem cells of female patients in Jordan, Cyprus and Israel (Arabs and Jews). In addition, the 3, 10, 5, 5 and 4 stage models are the optimal ones for the tumorigenesis of females in Egypt, Jordan, Cyprus, Israel (Arabs) and Israel (Jews), respectively. The genomic instability is caused by first three driver mutations.

Effector Avr4 in Phytophthora infestans Escapes Host Immunity Mainly Through Early Termination

Effector genes play critical roles in the antagonistic interactions between plants and pathogens. However, knowledge of mutation mechanisms and evolutionary processes in effector genes and the contribution of climatic factors to the evolution of effector genes are fragmented but important in sustainable management of plant diseases and securing food supply under changing climates. Here, we used a population genetic approach to explore the evolution of the Avr4 gene in Phytophthora infestans, the causal agent of potato blight. We found that the Avr4 gene exhibited a high genetic diversity generated by point mutation and sequence deletion. Frameshifts caused by a single base-pair deletion at the 194th nucleotide position generate two stop codons, truncating almost the entire C-terminal, which is important for effector function and R4 recognition in all sequences. The effector is under natural selection for adaptation supported by comparative analyses of population differentiation (FST) and isolation-by-distance between Avr4 sequences and simple sequence repeat marker loci. Furthermore, we found that local air temperature was positively associated with pairwise FST in the Avr4 sequences. These results suggest that the evolution of the effector gene is influenced by local air temperature, and the C-terminal truncation is one of the main mutation mechanisms in the P. infestans effector gene to circumvent the immune response of potato plants. The implication of these results to agricultural and natural sustainability in future climate conditions is discussed.

Mutation Mechanisms of Breast Cancer among the Female Population in China

Background: Cancer is a genetic disease caused by the accumulation of gene mutations. It is important to derive the number of driver mutations that are needed for the development of human breast cancer, which may provide insights into the tumor diagnosis and therapy. Objective: This work is designed to investigate whether there is any difference for the mutation mechanism of breast cancer between the patients in the USA and those in China. We study the mechanisms of breast cancer development in China, and then compare these mechanisms with those in the USA. Methods: This work designed a multistage model including both gene mutation and clonal expansion of intermediate cells to fit the dataset of breast cancer in China from 2004 to 2009. Results: Our simulation results show that the maximum number of driver mutations for breast epithelium stem cells of females in China is 13 which is less than the 14 driver mutations of females in the USA. In addition, the two-hit model is the optimal one for the tumorigenesis of females in China, which is also different from the three-hit model that was predicted as the optimal model for the tumorigenesis of females in the USA. Conclusion: The differences of the mutation mechanisms between China and the USA reflect a variety of lifestyle, genetic influences, environmental exposure, and the availability of mammography screening.