Table 2

Germline mutations identified in patients with therapy related myeloid neoplasms

UPNGeneMutationPredicted effectPedigreePrevious description
5869BRCA1
  • c.3112G>T

  • p.E1038*

  • rs80357161

Truncating mutation (NMD), clinically important (BIC)HBOCSOne entry in BIC
5824BRCA1
  • c.5251C>T

  • p.R1751*

  • rs80357123

Truncating mutation (NMD), clinically important (BIC)HBOCSMultiple entries in BIC
5298BRCA2
  • c.4027A>G

  • p.K1343E

Benign (PP2); tolerant (SIFT); polymorphism, protein features (might be) affected, splice site changes (MT)Inconspicuous, identified by systematic screeningNone
6387BARD1
  • c.1670G>C

  • p.C557S

  • rs28997576

Reduced capability of growth suppression and apoptosisHBOCSSauer et al27
4353Unknown
5650TP53
  • g.18508_18761delinsGCC

  • c.782+143_835delinsGCC

Pathogenic; mutation involves splice site, protein structure unknownInconspicuous, but patient fulfils LFL criteriaNone
6371TP53
  • c.845_848dupGGCG

  • p.R283fs*22

Truncating mutation (NMD), predicted disease causing (MT)Multiple diverse neoplasmsNone
6144TP53
  • c.1146delA

  • p.K382fs*40

Prolonged p53 (+27 AA), predicted disease causing (MT)InconspicuousSomatic mutation in a gastric cancer cell line (COSMIC) and EBV transformed lymphoblasts28
7047TP53
  • c.847C>T

  • p.R283C

Deleterious (TMD)Inconspicuous, identified by comprehensive screeningMultiple entries in TMD and COSMIC
  • dbSNP build 131; NM_007294.3 (BRCA2); NG_017013.1, NM_000546.4 (TP53).

  • BIC, breast cancer information core database; EBV, Epstein-Barr virus; HBOCS, hereditary breast and ovarian cancer syndrome; LFL, Li-Fraumeni like syndrome; MT, MutationTaster; NMD, nonsense mediated mRNA decay; PP2, PolyPhen-2; SIFT, Sorting Tolerant From Intolerant algorithm; TMD, IARC TP53 Mutation Database; UPN, unique patient number.