الملخص الإنجليزي
Background: In Oman, 53.5% of women are diagnosed with breast cancer (BC)
before the age of 50 compared to western countries where the median age of patients
diagnosed with BC is 65 years. Younger patients have a worse outcome in terms of
prognosis and survival with more aggressive behavior than older patients. However,
the reasons behind this statement were not studied well and the factors that affect the
age of diagnosis of BC yet unknown. Objective: This study is focusing on
understanding the tumor genetics difference between early-onset and late-onset breast
cancer patients of Omani cohort before the treatment and discovering new biomarkers
and therapeutic targets mainly for young BC patients, then comparing our data with
publicly available data of western BC populations. Materials and Methods: Whole
genome sequencing using Oncomine Comprehensive Assay Plus was carried out for
38 BC patients' tissues and all genes with mutations and variations were identified and
the analysis of genes difference between the younger and older groups was determined
using different statistical tools. Multivariate and univariate analysis was conducted to
determine the association between the altered genes and clinicopathological
characteristics of the patients' cohort. The expression level of the most common genes
in the tumor tissues of cases was studied using quantitative real-time PCR and the five years overall survival analysis of the patients in correlation with the altered genes was
performed using Kaplan–Meier procedure. cBioPortal database was used for
comparing our data with other published studies. Results and discussion: A total of
387 genomic alterations of different types were identified in Omani BC patients'
cohort. The alteration of FAM186A, ASXL1, CCNE1, NOTCH2, and other genes was
detected only in early-onset cases. The genes CDK12, ERBB2, SPOP, and RNF43 were
varied significantly with higher copy number in early-onset cases compared to post menopausal cases. Thus, they could be effective therapeutic targets for younger Omani
BC cases. Genes such as RECQL4, TP53, FGFR family, CBFB, CDH1, and other
genes were significantly associated with tumor size T2, grade 3, lymph nodes N2,
luminal A subtype and histological differentiation, respectively. The relative
expression of CUL4A and AKT1 was significantly upregulated in the young tumor
tissue compared to older patients. The genes such as RPS6KB1, RAD51C, and NBN
were significantly associated with lower overall survival compared to wild type tumor
(p<0.05) while TP63 and AURKA mutation was significantly associated with an
improved overall survival. Conclusion: This study is a comprehensive genomic
analysis to explore the association between the age and genes variation for precise
treatment decision for Omani BC patients in the future.
