Open AccessRevertant somatic mosaicism as a cause of cancer
Author(s) -
Inaba Toshiya,
Nagamachi Akiko
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14852
Subject(s) - somatic cell , cancer research , haploinsufficiency , bone marrow , medicine , leukemia , myelodysplastic syndromes , monosomy , myeloid , myeloid leukemia , mutation , biology , genetics , immunology , chromosome , gene , phenotype , karyotype
Revertant (somatic) mosaicism is a spontaneous correction of a causative mutation in patients with congenital diseases. A relatively frequent event, revertant mosaicism may bring favorable outcomes that ameliorate disorders, and is therefore called “natural gene therapy.” However, it has been revealed recently that “overcorrection” of inherited bone marrow failure in patients with sterile alpha motif domain containing 9 (SAMD9)/9L syndromes by revertant mosaicism induces myelodysplastic syndrome (MDS) with monosomy 7 that occasionally proceeds to acute myelogenous leukemia (AML). In this review, we interpret very complex mechanisms underlying MDS/AML in patients with SAMD9/9L syndromes. This includes multiple myeloid tumor suppressors on the long arm of chromosome 7, all of which act in a haploinsufficient fashion, and a difference in sensitivity to interferon between cells carrying a mutation and revertants. Overcorrection of mutants by somatic mosaicism is likely a novel mechanism in carcinogenesis.