MRC1 and neoplasm: MMR gene dosage, which affects the extent and degree of the MMR defect, is also important, both constitutionally (for example, biallelic germline mutations are associated with a distinct tumor spectrum characterized by hematological and central nervous system malignancies, [42]) and somatically (for example, DNA damage signaling requires a higher dosage of MMR protein than DNA mismatch repair [43] and inactivation of both alleles of a MMR gene may, therefore, not always be necessary in tumor cells).