PREDICTIVE AND PROGNOSTIC SIGNIFICANCE OF PALB2 GENE MUTATIONS IN BREAST TUMORS
Authors:
Type:
Сonference abstract
Published:
16.02.2023
Subject area:
UDK 61 Медицина. Охрана здоровья. Пожарное дело
Language:
Russian
Keywords:
PALB2, DNA copy number aberrations, mutations, chemotherapy efficacy, prognosis
Abstract (English):
It has been shown that the loss of PALB2 function, due to mutations or chromosomal aberrations, may have an impact on the effectiveness of chemotherapy treatment and disease prognosis in patients with various oncological diseases. Thus, the aim of this work was to evaluate the predictive and prognostic potential of DNA copy number aberrations and PALB2 gene mutations in breast tumors. Materials and methods. The study included 66 patients with breast cancer (BC). To evaluate the presence of DNA copy number aberrations (CNA), microarray analysis was used with the CytoScanTMHD Array high density microarrays. Gene mutations were assessed by sequencing on the MiSeq™ Sequencing System using the Accel-Amplicon BRCA1, BRCA2, and PALB2 Panel. Results. The presence of the PALB2 CNA gene is not associated with the effectiveness of neoadjuvant chemotherapy (NAC), p=0.07. The presence of a deletion is determined by 100% metastatic-free survival, versus 68% in the group with normal copy number (log-rank test p=0.04). It has been established that elimination of the frameshift deletion c.2552delA mutation during NAC leads to an objective response to treatment. Identified missense mutations (c.2993G>A; c.2014G>C; c.1010T>C) were observed in patients with tumor progression. But only c.1010T>C has pathogenic significance. The presence of mutations in the PALB2 gene is not associated with metastatic survival (log-rank test p=0.15). Conclusion. Currently, there is little data on the impact of disorders in the PALB2 gene on the effectiveness of treatment and prognosis of the disease, but the study of this gene has great potential for testing focused on diagnosis, prevention, and a personalized approach to the treatment of cancer patients
It has been shown that the loss of PALB2 function, due to mutations or chromosomal aberrations, may have an impact on the effectiveness of chemotherapy treatment and disease prognosis in patients with various oncological diseases. Thus, the aim of this work was to evaluate the predictive and prognostic potential of DNA copy number aberrations and PALB2 gene mutations in breast tumors. Materials and methods. The study included 66 patients with breast cancer (BC). To evaluate the presence of DNA copy number aberrations (CNA), microarray analysis was used with the CytoScanTMHD Array high density microarrays. Gene mutations were assessed by sequencing on the MiSeq™ Sequencing System using the Accel-Amplicon BRCA1, BRCA2, and PALB2 Panel. Results. The presence of the PALB2 CNA gene is not associated with the effectiveness of neoadjuvant chemotherapy (NAC), p=0.07. The presence of a deletion is determined by 100% metastatic-free survival, versus 68% in the group with normal copy number (log-rank test p=0.04). It has been established that elimination of the frameshift deletion c.2552delA mutation during NAC leads to an objective response to treatment. Identified missense mutations (c.2993G>A; c.2014G>C; c.1010T>C) were observed in patients with tumor progression. But only c.1010T>C has pathogenic significance. The presence of mutations in the PALB2 gene is not associated with metastatic survival (log-rank test p=0.15). Conclusion. Currently, there is little data on the impact of disorders in the PALB2 gene on the effectiveness of treatment and prognosis of the disease, but the study of this gene has great potential for testing focused on diagnosis, prevention, and a personalized approach to the treatment of cancer patients
Keywords:
PALB2, DNA copy number aberrations, mutations, chemotherapy efficacy, prognosis
PALB2, DNA copy number aberrations, mutations, chemotherapy efficacy, prognosis
1. PREDIKTIVNAYa I PROGNOSTIChESKAYa ZNAChIMOST' MUTACIY GENA PALB2 V OPUHOLI MOLOChNOY ZhELEZY
