Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, characterized by high tumor heterogeneity and a poor prognosis. Inter- and intra-tumoral heterogeneity in PDAC is a major obstacle to effective PDAC treatment; therefore, it is highly desirable to explore the tumor heterogeneity and underlying mechanisms for the improvement of PDAC prognosis. Gene copy number variations (CNVs) are increasingly recognized as a common and heritable source of inter-individual variation in genomic sequence. In this review, we outline the origin, main characteristics, and pathological aspects of CNVs. We then describe the occurrence of CNVs in PDAC, including those that have been clearly shown to have a pathogenic role, and further highlight some key examples of their involvement in tumor development and progression. The ability to efficiently identify and analyze CNVs in tumor samples is important to support translational research and foster precision oncology, as copy number variants can be utilized to guide clinical decisions. We provide insights into understanding the CNV landscapes and the role of both somatic and germline CNVs in PDAC, which could lead to significant advances in diagnosis, prognosis, and treatment. Although there has been significant progress in this field, understanding the full contribution of CNVs to the genetic basis of PDAC will require further research, with more accurate CNV assays such as single-cell techniques and larger cohorts than have been performed to date.

Keywords: copy number variations (CNVs); non-allelic homologous recombination (NAHR); pancreatic ductal adenocarcinoma (PDAC); patient stratification.

Figure 1

Non-allelic homologous recombination (NAHR). (A) Normal alignment of homologous chromosomes. (B) Misalignment of homologous chromosomes before crossing over, for example, due to abnormal pairing between repetitive sequences with high sequence identity. (C) Duplication and deletion that result from the unequal crossing over.

Figure 2

Associations in the development of pancreatic cancer, including the relationship between PDAC and copy number variations (CNVs).

Figure 3

A flow chart of the identification process of the included articles: 258 papers were initially identified by title, of which 41 fulfilled the inclusion criteria after full-text evaluation. A total of 41 papers were included.