The scientific advances of recent years have allowed us to understand in detail many genetic aspects of cancer. A first distiction should be done between germline mutations, which cause a strong
susceptibility to the onset of particular tumor types, commonly but
erroneously called hereditary, and somatic mutations, most often the consequence and not
the primary cause of the presence of tumor.
In principle it would be correct to say that all cancers have somatic mutations, but not all tumors have germline mutations.
Somatic mutations accumulate at at each cell division, leading to the formation of multiple clones of tumor cells. The cells belonging to each clone are genetically identical, but different from those of the other clones. Some clones can thus develop different proliferative and biological charcteristics, for example with respect to the risk of metastasis or responsiveness to certain drugs .
Genetic test in oncology can have essentially two purposes : (1) identification of genetic susceptibility to certain types of cancer, (2) identification of the most appropriate treatment in some subtypes of cancer.
Types of biological genetic mutation of tumor cells
Even in tumor cells, as well as in all the other cells, genetic mutations can be classified in terms of "size" in two large categories: genic mutations and chromosomal mutations. Genic mutations are smaller (but not for this are less severe), being constituted by variations of one or few nucleotides of the sequence. Chromosomal mutations are much larger, consisting of aberrations in number or structure of (part of) entire chromosomes. Chromosomal aberrations typical of tumors are fusion genes (fusion genes) , translocations and quantitative abnormalities (duplications, multiplications, deletions, also known as copy number variations, or CNVs ) .
When is genetic testing appropriate?
From a clinical point of view , it is good to distinguish between immediate benefit to the patient and primary advantage for scientific research. There are genetic tests that can help diagnose a real genetic susceptibility or to choose the best treatment. This does not mean that, at least at present, genetic testing is indicated in all cases of malignant disease . If it is true that genetics are a fundamental aspect of cancer biology, it must be remembered that in many cases genetic mutations are a consequence rather than a cause of the presence of the tumor. In most cases cancer is a sporadic disease and not an inherited disease. Just think about carcinogenic factors (smoking, benzene, radioactive substances, special chemicals, etc.), of which action leads to severe mutations in cellular DNA : these are typical (and frequent) examples of genetic mutations being consequence and not primaru cause of the tumor. However, there is a minority of tumors (as already mentioned quite small indeed) whose genesis is related to a strong genetic susceptibility. So to answer the question of when genetic testing is indicated:
1 . Genetic test for somatic mutation detection: for some particular types of tumor can be indicated in order to identify a pattern of optimal treatment (some types of cell clones may respond better to one drug rather than to another )
2 . Genetic test for germline mutation detection: indicated to identify any profiles of strong genetic susceptibility to the development of some forms of cancer.
What methods exist to identify genetic mutations in cancer?
Traditionally, genic mutations are investigated by methods of molecular genetics, while chromosomal ones by cytogenetic techniques (karyotype) or cytogenetics (FISH). To date, however, molecular genetics techniques have been made available to analyse both genic and chromosomal mutations.
In principle it would be correct to say that all cancers have somatic mutations, but not all tumors have germline mutations.
Somatic mutations accumulate at at each cell division, leading to the formation of multiple clones of tumor cells. The cells belonging to each clone are genetically identical, but different from those of the other clones. Some clones can thus develop different proliferative and biological charcteristics, for example with respect to the risk of metastasis or responsiveness to certain drugs .
Genetic test in oncology can have essentially two purposes : (1) identification of genetic susceptibility to certain types of cancer, (2) identification of the most appropriate treatment in some subtypes of cancer.
Types of biological genetic mutation of tumor cells
Even in tumor cells, as well as in all the other cells, genetic mutations can be classified in terms of "size" in two large categories: genic mutations and chromosomal mutations. Genic mutations are smaller (but not for this are less severe), being constituted by variations of one or few nucleotides of the sequence. Chromosomal mutations are much larger, consisting of aberrations in number or structure of (part of) entire chromosomes. Chromosomal aberrations typical of tumors are fusion genes (fusion genes) , translocations and quantitative abnormalities (duplications, multiplications, deletions, also known as copy number variations, or CNVs ) .
When is genetic testing appropriate?
From a clinical point of view , it is good to distinguish between immediate benefit to the patient and primary advantage for scientific research. There are genetic tests that can help diagnose a real genetic susceptibility or to choose the best treatment. This does not mean that, at least at present, genetic testing is indicated in all cases of malignant disease . If it is true that genetics are a fundamental aspect of cancer biology, it must be remembered that in many cases genetic mutations are a consequence rather than a cause of the presence of the tumor. In most cases cancer is a sporadic disease and not an inherited disease. Just think about carcinogenic factors (smoking, benzene, radioactive substances, special chemicals, etc.), of which action leads to severe mutations in cellular DNA : these are typical (and frequent) examples of genetic mutations being consequence and not primaru cause of the tumor. However, there is a minority of tumors (as already mentioned quite small indeed) whose genesis is related to a strong genetic susceptibility. So to answer the question of when genetic testing is indicated:
1 . Genetic test for somatic mutation detection: for some particular types of tumor can be indicated in order to identify a pattern of optimal treatment (some types of cell clones may respond better to one drug rather than to another )
2 . Genetic test for germline mutation detection: indicated to identify any profiles of strong genetic susceptibility to the development of some forms of cancer.
What methods exist to identify genetic mutations in cancer?
Traditionally, genic mutations are investigated by methods of molecular genetics, while chromosomal ones by cytogenetic techniques (karyotype) or cytogenetics (FISH). To date, however, molecular genetics techniques have been made available to analyse both genic and chromosomal mutations.
