Table 1.
PAX5 alterations in B-ALL.
| Cohort | Platform | Comments on PAX5 alteration | Ref. |
|---|---|---|---|
| 242 pediatric ALL | SNP array | PAX5 gene is the most frequent target of somatic mutation, being altered in 31.7% of cases. | (1) |
| 40 pediatric ALL | SNP array | Cell cycle and B cell related genes, including PAX5, are the most frequent mutated genes. | (2) |
| 304 ALL samples | SNP array | Deletion of PAX5 in 51% BCR::ABL1 cases, of which 95% have a deletion of IKZF1. | (3) |
| 61 pediatric B-ALL (diagnosis & relapse) |
SNP array | Around 50% of B-ALL have CNAs in genes known to regulate B-lymphoid development, especially in PAX5 and IKZF1 genes. | (4) |
| 399 pediatric ALL | SNP array | 7 cases harbor PAX5 fusions. | (5) |
| 221 pediatric B-ALL (high-risk) |
SNP array, GEP array, target sequencing | PAX5 CNA is involved in 31.7% of patients; P80R is the most frequent mutation. | (6) |
| 466 pediatric ALL | FISH | PAX5 rearrangements occur in 2.5% of B-ALL. | (7) |
| 117 adult B-ALL | FISH, qPCR, target sequencing | PAX5 is mutated in 34% of adult B-ALL. P80R is the most frequent point mutation. PAX5 deletion is a secondary event. | (8) |
| 153 adult and pediatric B-ALL with 9p abnormalities | SNP array, FISH | PAX5 has internal rearrangements in 21% of the cases. Malignant cells carrying PAX5 fusion genes displayed a simple karyotype. | (9) |
| 89 Ph+ B-ALL | SNP array | PAX5 genomic deletions were identified in 29 patients (33%). In all cases, the deletion was heterozygous. | (10) |
| Two B-ALL families | WES, SNP array | Germline PAX5 G183S confers susceptibility to B-ALL. | (11) |
| 116 B-ALL | MLPA | 5 cases with PAX5 intragenic amplifications were identified. | (12) |
| One B-ALL family | SNP array | A third B-ALL family carrying germline G183S mutation. | (13) |
| 798 adult B-ALL | GEP array, SNP array, RNA-seq | 38% of Ph-like B-ALL have PAX5 alterations. Enrichment of CNA of IKZF1, PAX5, EBF1, and CDKN2A/B observed in the Ph-like subtype. | (14) |
| 79 B-ALL with PAX5 iAmp | MLPA, FISH, SNP array | PAX5 iAmp defines a novel, relapse-prone subtype of B-ALL with a poor outcome. | (15) |
| 1,988 B-ALL | RNA-seq, WGS, WES, SNP array | Detailed description of PAX5 alterations in B-ALL. Defined the PAX5alt and PAX5 P80R subtypes. | (16) |
| 110 pediatric B-others | RNA-seq, WES, SNP array | PAX5 fusions, iAmp and P80R mutations are mutually exclusive, altogether accounting for 20% of the B-other group. PAX5 P80R is associated with a specific gene expression signature. | (17) |
| 250 B-ALL | DNA methylation array, WES, RNA-seq | 16 patients with P80R grouped into an individual subgroup with biallelic PAX5 alterations. | (18) |
| 1,028 pediatric B-ALL | SNP array | 20 cases of PAX5 P80R with intermediate or poor outcome compared to the rest of this cohort. | (19) |
| One B-ALL family | WES, RNA-seq | PAX5 R38H germline mutation was identified in a family with B-ALL. | (20) |
CNA, copy number alterations; GEP, gene expression profile; WGS, whole genome sequencing; WES, whole exome sequencing; FISH, fluorescence in situ hybridization; MLPA, multiplex ligation-dependent probe amplification; RNA-seq, whole transcriptome sequencing.