Genomic Copy Number Alterations in Serous Ovarian Cancer

Abstract

Precision medicine in cancer is the idea that the recognition and targeting of key genetic drivers of a patient's tumor can permit more effective and less toxic outcomes. Point mutations that alter protein function have been primary targets. Yet in ovarian cancer, unique genetic mutations have been identified only in adult granulosa cell tumors, with a number of other point mutations present in mucinous, clear cell and endometrioid carcinoma subtypes. By contrast, the serous subtype of ovarian cancer shows many fewer point mutations but cascading defects in DNA damage repair that leads to a network of gains and losses of entire genes called somatic copy number alterations. The shuffling and selection of the thousands of genes in serous ovarian cancer has made it a complex disease to understand, but patterns are beginning to emerge based on our understanding of key cellular protein networks that may provide a better basis for future implementation of precision medicine for this most prevalent subtype of disease.

Characterization of BRCA Deficiency in Ovarian Cancer

“…Genomic rearrangements were assessed in a subgroup of samples in order to compare BRCA-deficient with non-deficient tumors. The analysis of deletions and duplications did not lead to statistically significant differences between BRCA intact and defective cancers; as already reported for serous OC [36], highly rearranged genomes were found, both in BRCA intact and defective cancers, with a complex heterogeneity of cellular clones with different chromosomal anomalies that cannot be fully appreciated and precisely defined by array-CGH. However, when the analysis was extended to small CNVs (>1 Mb and <10 Mb), the frequency, especially of duplications, was significantly higher in OC with BRCA deficiency, which is consistent with a previous report [37].…”

Spontaneous Transformation of a p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line after Long Passage with Features of High-Grade Serous Carcinoma

“…Comparative genomic hybridization revealed that CCNE1 was significantly amplified [45]. Nevertheless, few additional single-gene drivers have been explored in TCGA [16,46]. Our study also found more CNV amplifications of ERBB2, TP53, and CCNE1 in FE25L than in FE25 cells.…”