Application of DNA fingerprints to identify mutational signatures

Cancer and its causes

The major cause of cancer is found to be some unwanted changes in the structure of DNA that are otherwise called as mutations, inducing uncontrollable cell division. There are many reasons of cancer, such as lack of fidelity of the DNA replication machinery, disclosures to mutagen, enzymatic DNA alteration, and faulty repair of DNA that results a definite fingerprint on DNA damage. All the cells of human body possess somatic mutations throughout life.

What are mutational signatures?

There are certain mutational patterns within the cancerous gene that are now being revealed including the complication of somatic mutation. Several mutations create specific arrangements of mutation types, designated “Mutational Signatures”. Due to increase in the quantity of sequenced whole-genome and refined analytical methods, it is possible to extract more mutational signatures along with more exact definition of their structures.

These fingerprints help in understanding the development of cancer and their prevention. Extensive analyses have discovered numerous mutational signatures in human cancer kinds. However, previous researches were not sufficient to recognize all probable mutational signatures.

Identification of mutational signatures by DNA fingerprinting

Mutations are of various types, starting from single nucleotide mutations to deletion or insertion of a chain of nucleotides resulting in genetics changes. These changes can act as mutational signatures to be identified by DNA fingerprinting. The consequence is the prevalent database of reference mutational signatures ever. Half of all the mutational signatures have identified reasons, but this source could find more causes and understand cancer development in a better way. Certain mutational signatures, or DNA fingerprints, reveal the cancer response to drugs.

 Future prospective

The foundation of certain signatures is accepted, however, for several it remains hypothetical or indefinite. Explaining the mutational processes will be influenced by two key investigations. At first, mutational signatures accumulation from model systems, exposed to known mutagens or disturbances of the DNA maintenance machinery and assessment with those found in human cancers. Second, the association of the causes of mutational signatures with other biological characteristics of each cancer through varied methods extending from molecular profiling to epidemiology. Jointly, the researches will develop the cancer aetiology understanding with possible suggestions for prevention and management.

Advance bioinformatics tool tests approaches for identification of cancer genes

Being a complex genetic disease, cancer is resulted predominantly due to mutations in somatic cells of the genome. Mutations in the somatic cells may imbalance definite cell cycle process causing the attainment of cellular susceptibilities that convert a healthy cell to a cancerous cell. These changes drive cancer instigation and development. Additionally, they comprise of inactivating growth suppressors, counterattacking cell death, and further irregular phenotypes. As cancer is related with the genome disorder, hence it is practical that treatment approaches must be established on changes in genomic structure.

Numerous changes in somatic cells which are considered as mutation induce as well as promote tumor growth, and most of these genetic changes are being detected by the scientists of cancer genomics.

Traditional experimental approaches

Numeroussomatic mutations are being reported applying low‐throughput approaches, including systematic mutagenesis, cytogenetic techniques, genetic linkage analysis, and targeted gene sequencing. Conversely, all of the outdated methods are tiresome, cumbersome, and expensive.

Next-generation sequencing (NGS) in cancer genomics analysis

Next-generation sequencing detects the driver‐genes, with mutations leading the resistance to drugs. Furthermore, it can be applied to sense hypermutation that is likely to be important biomarker for immune checkpoint inhibitors. This also defines changes in double‐strand break repair pathway of DNA that is an evolving objective for novel treatments, and like wise-diligently linked to genetic genomic changes. Certain biological pathways along with a group of cancer‐associated genes (mutated genes) are being compared to pre-established biological pathways. Methods which are based on network search for cancer genes and biological pathways that characterize the interactions between cellular molecules. Methods learning pathways de novo do not utilize any previous information about the genes (interactions or pathways) and deduce cancer genes and pathways based on the forms of co‐occurrence or mutual individuality between the genetic abnormalities.

Methods for detecting novel cancer genes

Identification of unusual cancerous genes initiates with tumor samples sequenced. The major step is to distinguish genetic mutations using variant callers from sequencing data. The easiest methods to achieve this are by noticing recurring variations and by forecasting the practical influence of every mutation. The approaches can be classified mainly within 3kinds: (a) that utilize established paths, (b) those are founded on current biological system facts, and (c) envisaging cancer pathways de novo founded on the combinatorial forms of incidence in tumors group.


There are numerous issues to be addressed so as to perform efficiently in future cases.  High cost is the major issue of NGS. The NGS‐based gene panel experiments charge several thousand US dollars per sample, and the whole genome sequencing costs more than NGS.

After the analysis in NGS, the further task is to understand the data and choose the therapeutic agent which will mostly be appropriate by linking gene alteration information along with scientific data. Presently the work is in progress in Japan and other developed countries. There are huge, online accessible genomic databases; but, the quantity of the data associated with medical cure outcomes is as yet inadequate.