There are A)rare high penetrance autosomal dominant mutations in cancer predisposition genes that require different surveillance B) moderate risk genes where less is known about the penetrance and likely modifiers of their ultimate lifetime risk C) there are variations in many genes with minor effect on penetrance and their impact, singly or multiplicatively, is still emerging. Given the recent advances in sequencing technology testing multiple genes costs less than the price of one gene 5 years ago. Just because testing is possible does NOT mean the tests are useful and advantageous.
Colorectal cancer is the poster child for personalised medicine because simple immune-histochemical stains on the original histology specimen, allows identification of 1) the majority of patients with Lynch Syndrome (a condition caused by germline mutations in the mismatch repair genes MLH1 MSH2 MSH6 PMS2) 2)prognostic information and 3)gives an indication of treatments likely to be helpful. Relatives at risk can be tested and if they have the family mutation appropriate surveillance can be instituted and those without the family mutation do not need extra surveillance.
Proponents of large panels argue that the use of a 25 or 78 gene panel allows interrogation of genes considered based on 1) phenotype (APC, SMAD4, STK11, biallelic MUTYH TP53) as well as 2) moderate penetrance genes (ATM, CHEK2) 3) low penetrance genes (Monoallelic MUTYH and APC I1307K) as well as 4)genes not previously considered colorectal cancer predisposition genes including BRCA1 or BRCA2, PALB2, CDKN2A. However in the clinical setting, the disadvantages of the high rate of variant of uncertain clinical significance rate (30-45%), the prior probability of a mutation and the risk of inappropriate labelling of patients need to be considered as the cost effectiveness of panel testing in colorectal cancer has not yet been established.