Methods for determining the cause of somatic mutagenesis

A method for treating a cancer in a human subject, the method comprising:

• isolating a nucleic acid molecule from a biological sample obtained from a human subject;
• determining the sequence of the nucleic acid molecule;
• determining whether targeted somatic mutagenesis has occurred, wherein targeted somatic mutagenesis has occurred when there is a higher than expected percentage or number of mutations of a mutation type at one of three positions in a codon in a plurality of mutated codons in the nucleic acid molecule, wherein:
• the nucleic acid molecule comprises the whole exome;
• the mutations are at a motif recognized or targeted by APOBEC3G;
• and
• the number or percentage of observed G>A mutations in CG motifs at MC-2 sites in the non-transcribed strand of the nucleic acid molecule is higher than expected, or the number or percentage of observed C>T mutations in CG motifs at MC-1 sites in the non-transcribed strand of the nucleic acid molecule is higher than expected;
• selecting the subject as being likely to have cancer when targeted somatic mutagenesis has occurred;
• and
• exposing the subject to a therapy for treating the cancer;
• wherein the therapy comprises radiotherapy, surgery, chemotherapy, hormone ablation therapy, pro-apoptosis therapy and/or immunotherapy,
• thereby treating the cancer, wherein the cancer is selected from the group consisting of breast, prostate, liver, colon, pancreatic, skin, cervical, lymphoid, hematopoietic and ovarian cancer;
• and the biological sample comprises, respectively, breast, prostate, liver, colon, pancreatic, skin, cervical, lymphoid, hematopoietic or ovarian tissue or cells.