- Martin Granzow1,*,
- Ute Hegenbart2,
- Katrin Hinderhofer1,
- Dirk Hose2,
- Anja Seckinger2,
- Tilmann Bochtler3,
- Kari Hemminki4,
- Hartmut Goldschmidt5,
- Stefan O Schönland2 and
- Anna Jauch1
- 1 Institute of Human Genetics, Universität of Heidelberg, Heidelberg, Germany;
- 2 Department of Internal Medicine V, Universität of Heidelberg, Heidelberg, Germany;
- 3 Universität Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany;
- 4 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg,Germany;
- 5 Universitätsklinikum Heidelberg and National Center for Tumor Diseases (NCT),Heidelberg,Germany
- ↵* Corresponding author; email:
Immunoglobulin light chain amyloidosis is a rare plasma cell dyscrasia characterized by deposition of abnormal amyloid fibrils in multiple organs impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization. We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%), as well as 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by interphase fluorescence in situ hybridization was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by interphase fluorescence in situ hybridization almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in immunoglobulin light chain amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered.
- Received November 28, 2016.
- Accepted March 15, 2017.
- Copyright © 2017, Ferrata Storti Foundation