Molecular genetic diagnosis of familial tumors

Recent advances in molecular biology have identified the responsible genes for many hereditary cancer syndromes (familial tumors). Therefore, now, the final diagnosis of familial tumors can be done by molecular methods to detect the genetic alteration in the disease-causing responsible gene(s) in the patient. So-called "genetic testing" is now available, not only as the diagnosis in the proband but also as the pre-symptomatic carrier diagnosis for unaffected family members. However, a number of issues, including legal, ethical, social, psychological, economic, and technical ones, surround and inhibit the clinical application of this testing, especially in Japan. As for molecular analysis to detect possible mutation in clinical specimens, highly sensitive scanning and detection methods are indispensable for screening nucleotide substitutions, including point mutations and single-nucleotide polymorphisms (SNPs). Also, several methods have been developed to screen and confirm the genetic alterations in familial tumors. These analytical techniques for detecting genetic alterations are categorized into four types, involving (1) scanning of nucleotide substitutions, (2) detection of defined mutations or SNPs, (3) size determination, and (4) DNA sequencing. Each technique has its advantages and disadvantages, and the technique in each case should be selected according to the purpose of the analysis. In this article, the concept of molecular diagnosis in familial tumors and the related molecular methods are described.