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Comparative Study
. 2016 Mar 17;127(11):1512-5.
doi: 10.1182/blood-2015-12-685925. Epub 2016 Jan 29.

Uncompromised 10-year survival of oldest old carrying somatic mutations in DNMT3A and TET2

Erik B van den Akker  1 , Steven J Pitts  2 , Joris Deelen  3 , Matthijs H Moed  4 , Shobha Potluri  2 , Jeroen van Rooij  5 , H Eka D Suchiman  4 , Nico Lakenberg  4 , Wesley J de Dijcker  4 , André G Uitterlinden  6 , Robert Kraaij  6 , Albert Hofman  7 , Anton J M de Craen  8 , Jeanine J Houwing-Duistermaat  9 , Gert-Jan B van Ommen  10 ; Genome of The Netherlands Consortium; David R Cox  2 , Joyce B J van Meurs  5 , Marian Beekman  3 , Marcel J T Reinders  11 , P Eline Slagboom  3
Affiliations
Comparative Study

Uncompromised 10-year survival of oldest old carrying somatic mutations in DNMT3A and TET2

Erik B van den Akker et al. Blood. .
No abstract available

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Figures

Figure 1
Figure 1
Characterization of identified variants in blood of the RS and LLS elderly subsample. (A) Mutations in genes previously linked to hematopoietic malignancies. Barplot of the number of individuals carrying a mutation, split by genes and study. Note that only 11 of the 15 investigated genes had a mutation (see supplemental Appendix 4 for a complete list). (B) Prevalence of carriers of somatic mutations stratified by age category using data of Xie et al and the observations in the RS and LLS elderly subsample. (C) Distribution of VAFs of the identified mutations. (D) Comutation plot of carriers with 2 independent mutations. (E) Overview of mutations in DNMT3A identified in the RS and LLS elderly subsample. Variants are annotated at the top with color coding to indicate the impact and a shape to indicate the types of follow-up experiments. Circles indicate mutations detected in our sequencing data; squares indicate mutations also validated by Sanger sequencing; diamonds indicate mutations also validated by Sanger sequencing and absent in an IBD2 matched sib, that is, confirming somatic variations. Mutations identified in multiple carriers are indicated with stacked annotations and those having bold borders were identified in the LLS. Missense variants are only included whenever they are present on a curated list of recurrently reported variants in the Catalogue Of Somatic Mutations In Cancer (COSMIC) assembled by Jaiswal et al. Domains: ADD, histone-binding domains; DNMT, DNA methyltransferase interaction domain; MTase, methyltransferase domain; PWWP, conserved DNA binding domain; ZC-FING, zinc finger domains. COSMIC, densities of somatic variants identified in hematopoietic or lymphoid tissue collected by the Catalogue Of Somatic Mutations In Cancer (COSMIC) database: all small variants (red), missense single nucelotide variants (SNVs) (gray), small variants confirmed to be of somatic origin (blue).
Figure 2
Figure 2
Kaplan-Meier survival curves of the RS and LLS elderly subsample. (A) Kaplan-Meier curves for the 39 mutation carriers and 596 noncarriers in the RS elderly subsample. (B) Kaplan-Meier curves for the 40 mutation carriers and 168 noncarriers in the LLS elderly subsample. Because Jaiswal et al and Genovese et al do not agree on the status of DNMT3A missense mutations, we excluded DNMT3A missense mutation carriers from noncarriers in both the RS and LLS elderly subsample (supplemental Tables 6-7). (C) Forest plot combining the Cox proportional hazards analyses in the RS and LLS elderly subsample.
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