Page 1560 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 86 Plasma Cell Neoplasms 1387

Average no.
500 Mutational load per patient
450 INDELS 120
NON-SILENT substitutions
400 Total no. of genes in screen 2462 SILENT substitutions
Number of variants 300 Cancer census* genes 2379 80
350
83
250
Non cancer census genes
200
40
150
100
50
0 0 1
PD5855 PD4285 PD5877 PD4284 PD5876 PD5880 PD5898 PD5900 PD5856 PD5885 PD5888 PD5869 PD5884 PD5897 PD5867 PD5893 PD5857 PD5875 PD5879 PD5891 PD5896 PD5901 PD4293 PD5872 PD5873 PD5886 PD5851 PD5850 PD5865 PD5852 PD5860 PD5864 PD5866 PD5887 PD5882 PD5862 PD5871 PD5878 PD5895 PD4283 PD5859 PD5870 PD4295 PD5853 PD5858 PD5881 PD5890 PD4299 PD5868 PD4300 PD5892 PD5883 PD5894 PD5899 PD4288 PD5861 PD4301 PD4286
A Patient
No change
1.5 ROBO1
Early = Late Fertilized egg
Subcl. fraction late 1.0 TP53 100% tumor cells
48 mutations
Hyperdiploid;
1p-; ROBO1
0.5
common ancestor
61% tumor cells Most recent
6 mutations
0.0 TP53
0.0 0.5 1.0 1.5
Subcl. fraction early
Linear evolution
1.5 Early Late
100% tumor cells
BRAF Hyperdiploid; -13; KRAS
34 mutations
Subcl. fraction late
1.0
0.5
KRAS 15% tumor cells 15% tumor cells
15 mutations 15 mutations
NF1 NF1
0.0 NF1 41% tumor cells
20 mutations
0.0 0.5 1.0 1.5 BRAF
Subcl. fraction early
Differential clonal response
1.5 Early Late
100% tumor cells
CD79A Hyperdiploid; 1p-;
56 mutations
Subcl. fraction late 0.5 +1q; BRAF
1.0
Recurrent BRAF
Recurrent 10 –15%,5 0.0 25% tumor cells 5% tumor cells
5 –10%, 23 39 mutations 39 mutations
CD79A
Recurrent 0.0 0.5 1.0 1.5 CD79A 51% tumor cells 86% tumor cells
>20%,1 Subcl. fraction early 56 mutations 56 mutations
Branching evolution
Recurrent
<5%, 367 1.5
TP53 Early 100% tumor cells Late
20 mutations
Hyperdiploid
Subcl. fraction late 96% tumor cells
1.0
7 mutations
Unique, 0.5 17p- 98% tumor cells
11 mutations
2066 Hom. Del of
0.0 69% tumor CDKN2C 61% tumor cells
cells 4 mutations
0.0 0.5 1.0 1.5 8 mutations
TP53
Subcl. fraction early
B Bolli et al Nature Comm 2014
Fig. 86.3 (A) Total number of validated somatic variants for each patient in the cohort (top left), average
number of somatic variants per patients (top right), and frequency of unique and recurrent mutations (bottom
left). Two-dimensional density plots show the clustering of the fraction of tumor cells carrying each mutation
(black dots) at each time point (x = early sample, y = late sample; increasing intensity of red indicates the
location of a high posterior probability of a cluster). Right: Phylograms representing the clonal composition
of the tumor at each time point, where the length of each branch is proportional to the size of the clone (i.e.,
the number of variants) and the width to its clonality (i.e., the proportion of cells bearing each variant).