Clonally related rearrangements from 6 progressively transformed germinal centers
Pt . | Cells . | Clone . | V gene . | Functionality . | Mutation frequency (%) . | Sequence variants . |
---|---|---|---|---|---|---|
2 | Ki67+ | C1 | 6 × VH 4-61 | + | 5.1-7.5 | 6/6 |
4 × Vκ A17 | − | 0 | 0/4 | |||
4 × Vκ B3 | − | 0.4 | 0/4 | |||
5 × Vλ 1a | + | 4.5-5.6 | 4/5 | |||
C2 | 2 × Vλ 3h | + | 0.8 | 0/2 | ||
C3 | 2 × VH 4-59 | + | 0-0.3 | 2/2 | ||
C4 | 2 × Vλ 1c3-150 | + | 0 | 0/2 | ||
Ki67+/− | C5 | 2 × Vλ3h | + | 0 | 0/2 | |
Ki67− | C6 | 2 × Vλ 1e | + | 0 | 0/2 | |
3 | Ki67+ | C1 | 4 × VH4-4 | + | 9.2-10.5 | 4/4 |
2 × VH2-70 | − | 9.1-9.4 | 2/2 | |||
5 × VκL12 | + | 4.8-6.7 | 5/5 | |||
Ki67− | C2 | 2 × Vκ A273-150 | − | 0 | 0/2 | |
4 | Ki67+ | C1 | 3 × VκL12 | + | 2.9-4.3 | 3/3 |
PTGC1 | C2 | 2 × VH3-11 | + | 0 | 0/2 | |
3 × VκO12/2 | + | 0 | 0/3 | |||
Ki67+ | C3 | 4 × VH 5-51 | + | 4.8-7 | 4/4 | |
PTGC2 | C4 | 3 × VH 4-34 | + | 7-9.1 | 3/3 | |
5 | Ki67+ | C1 | 19 × VH4-39 | + | 3.1-4.7 | 18/19 |
PTGC1 | 5 × Vκ L12 | + | 2.6-3.4 | 5/5 | ||
Ki67+ | C2 | 5 × VH4b | + | 8.5-11.9 | 5/5 | |
PTGC2 | 5 × VκL12 | + | 2.1-3.5 | 5/5 | ||
C3 | 2 × VκL12 | + | 1.7-3.1 | 2/2 |
Pt . | Cells . | Clone . | V gene . | Functionality . | Mutation frequency (%) . | Sequence variants . |
---|---|---|---|---|---|---|
2 | Ki67+ | C1 | 6 × VH 4-61 | + | 5.1-7.5 | 6/6 |
4 × Vκ A17 | − | 0 | 0/4 | |||
4 × Vκ B3 | − | 0.4 | 0/4 | |||
5 × Vλ 1a | + | 4.5-5.6 | 4/5 | |||
C2 | 2 × Vλ 3h | + | 0.8 | 0/2 | ||
C3 | 2 × VH 4-59 | + | 0-0.3 | 2/2 | ||
C4 | 2 × Vλ 1c3-150 | + | 0 | 0/2 | ||
Ki67+/− | C5 | 2 × Vλ3h | + | 0 | 0/2 | |
Ki67− | C6 | 2 × Vλ 1e | + | 0 | 0/2 | |
3 | Ki67+ | C1 | 4 × VH4-4 | + | 9.2-10.5 | 4/4 |
2 × VH2-70 | − | 9.1-9.4 | 2/2 | |||
5 × VκL12 | + | 4.8-6.7 | 5/5 | |||
Ki67− | C2 | 2 × Vκ A273-150 | − | 0 | 0/2 | |
4 | Ki67+ | C1 | 3 × VκL12 | + | 2.9-4.3 | 3/3 |
PTGC1 | C2 | 2 × VH3-11 | + | 0 | 0/2 | |
3 × VκO12/2 | + | 0 | 0/3 | |||
Ki67+ | C3 | 4 × VH 5-51 | + | 4.8-7 | 4/4 | |
PTGC2 | C4 | 3 × VH 4-34 | + | 7-9.1 | 3/3 | |
5 | Ki67+ | C1 | 19 × VH4-39 | + | 3.1-4.7 | 18/19 |
PTGC1 | 5 × Vκ L12 | + | 2.6-3.4 | 5/5 | ||
Ki67+ | C2 | 5 × VH4b | + | 8.5-11.9 | 5/5 | |
PTGC2 | 5 × VκL12 | + | 2.1-3.5 | 5/5 | ||
C3 | 2 × VκL12 | + | 1.7-3.1 | 2/2 |
In addition to the clonal rearrangements amplified at least twice and listed above, rearrangements were amplified once from several clonally related cells. Patient 2, C3, from the cell with the unmutated VH rearrangement, an unmutated Vκ and a mutated Vλ (2.5% mutation frequency) rearrangement. Patient 4, C1, from one cell an unmutated in-frame Vλ 2e rearrangement, from the second cell an unmutated out-of-frame VK A17 and an unmutated out-of-frame Vλ1g, and from the third cell an unmutated out-of-frame Vκ O11/1 rearrangement; C2, from one cell an unmutated, potentially functional VH rearrangement; C3, from one cell a potentially functional, mutated (3%) Vκ O12/2 rearrangement; C4, from one cell a potentially functional mutated (3.1%) Vλ 1b rearrangement. Patient 5, C1, from 2 cells an unmutated, potentially functional VKrearrangement, each; C2, from one cell an unmutated out-of-frame Vκ and a mutated, potentially functional VH(0.8%) rearrangement; C3, an unmutated, potentially functional VH rearrangement.
Because nonproductive VκJκ joints are usually inactivated by deletion of the Cκ gene and the κ enhancers and are thereby exempted from somatic hypermutation, the finding of unmutated Vκ genes in clones with otherwise mutated immunoglobulin rearrangements is not unusual.
Pt indicates patient; PTCG, progressively transformed germinal center.
Rearranged without N-nucleotide insertion. Thus, it cannot be excluded that these two rearrangements originated from two clonally unrelated cells.