Conclusion
These results are consistent with the hypothesis that changes in expression of specific genes contribute to transformation from normal lymphocytes to MBL and CLL.
Methods
To identify inherited changes in gene expression, a high-resolution DNA microarray was used to identify differentially abundant mRNAs in age-matched cases of F-MBL (n = 4), F-CLL (n = 2) and unaffected family relatives (F-Controls, n = 3) within one family. These were then compared to non-kindred controls (NK-Controls, n = 3) and sporadic CLL (S-CLL) cases (n = 6).
Results
Seven differentially abundant mRNAs were identified against similar genetic backgrounds of the family: GRASP and AC016745.3 were decreased in F-MBL and further decreased in F-CLL compared to F-Controls, whereas C11orf80 and METTL8 were progressively increased. PARP3 was increased in F-MBL compared to F-Controls but was decreased in F-CLL compared to F-MBL. Compared to F-Controls, levels of ROR1 and LEF1 were similarly increased in F-MBL and F-CLL. For six of the genes, there were no differences in mRNA levels between S-CLL and F-CLL; however PARP3 was higher in S-CLL.