Medical scientists successfully mapped the mutation map of P13K/AKT pathway in breast cancer population in China

Medical Network April 13th reporter learned from Fudan University Affiliated Tumor Hospital, director of breast surgery and director of Fudan University Cancer Research Institute Professor Shao Zhimin, Associate Professor Hu Xin, Chen Li and Dr. Yang Liu and other research teams for five years to explore research, For the first time, the gene mutation map of PI3K/AKT pathway in breast cancer population in China was drawn, and the "functional mutation" in the pathway gene was systematically interpreted and identified. Relevant research results were published online in Nature Newsletter on the 11th.

It is reported that there are a large number of signal pathways in the human body; many genes are concentrated on each pathway. The study focused on the PI3K/AKT signaling pathway involved in the regulation of tumor malignant transformation and drug resistance, and sequenced the exon of the mutations of seven genes including PIK3CA, PIK3R1, PTEN and AKT. The highest mutation frequency was found in PIK3CA, accounting for 44%. %, the mutation frequency of the PIK3R1 gene is 17%, and the simultaneous mutation of these two genes accounts for 9%. The research team compared the US tumor and cancer gene map and the tumor somatic cell mutation catalogue database and found that the frequency of PIK3CA mutation in Chinese breast cancer patients is comparable to that in Western databases, and the frequency of PIK3R1 gene mutation is significantly higher than that in Western population.

In order to further clarify which mutations in the PIK3CA and PIK3R1 genes cause breast cancer and drug resistance, the research team independently developed a functional mutation screening system and systematically targeted most of the mutation sites of the two genes. Functional research and identification. Studies have found that mutations at positions 39, 1049, 345, 1043, 1047 in the PIK3CA gene and mutations at positions 160, 329, and 560 in the PIK3R1 gene will result in malignant transformation of breast cells and chemotherapy. The drug epirubicin and the pathway inhibitor BKM120 developed resistance.

"Through this study, we were able to successfully predict the 'bad molecules' that cause rapid proliferation and resistance of breast tumor cells." Professor Shao Zhimin said that the in-depth study of the pathway will provide important justification for clinical drug use and future drug development for these targets, and at the same time vigorously promote comprehensive and precise treatment of breast cancer.