Clinical and molecular characteristics of B-CLL patients with the CDK6 rearrangement
. | . | Overall survival (y of follow-up) . | . | FISH analysis . | . | SB analysis . | |
|---|---|---|---|---|---|---|---|
| Patient . | Sex/age at diagnosis, y . | . | Karyotype . | CDK6 . | Ig . | . | |
| 1 | M/61 | Alive (6) | 46,XY,t(7;22)(q22;q11), del(13)(q13q14)[12]/46,XY[9] | Split | Igλ split | R | |
| 2 | M/79 | Alive (3) | 46,X,-Y,+12[1]/46,X,-Y,+12, t(7;14)(q21;q32)[16]/46,XY[3] | Split | IgH split | NA | |
| 3 | M/61 | Died (16) | 45,XY,t(2;7)(p11-12;q22),der(8) t(8;17)(p12;p11), -17[5]/47,XY, t(2;7),+5,+12[10]/46,XY[35] | Split | NA | R | |
. | . | Overall survival (y of follow-up) . | . | FISH analysis . | . | SB analysis . | |
|---|---|---|---|---|---|---|---|
| Patient . | Sex/age at diagnosis, y . | . | Karyotype . | CDK6 . | Ig . | . | |
| 1 | M/61 | Alive (6) | 46,XY,t(7;22)(q22;q11), del(13)(q13q14)[12]/46,XY[9] | Split | Igλ split | R | |
| 2 | M/79 | Alive (3) | 46,X,-Y,+12[1]/46,X,-Y,+12, t(7;14)(q21;q32)[16]/46,XY[3] | Split | IgH split | NA | |
| 3 | M/61 | Died (16) | 45,XY,t(2;7)(p11-12;q22),der(8) t(8;17)(p12;p11), -17[5]/47,XY, t(2;7),+5,+12[10]/46,XY[35] | Split | NA | R | |
FISH analysis was sequentially performed on the same mitosis with mixed Human BAC Clone GS119p5 and Clone GSI-552A1 (encompassing intron 1, exon 1, and 178 kbp upstream of the coding sequence of the CDK6 gene; Incyte Genomics, San Francisco, CA) and with IgH probes (Vysis, Downers Grove, IL) or Igλ probes (kindly provided by Reiner Siebert). The CDK6 gene was split between chromosomes 7 and 22 in FIO, between chromosomes 7 and 14 in DUP, and between chromosomes 2 and 7 in LAN. Igλ and IgH involvement was further demonstrated in patients 1 and 2, respectively. It may be noticed that the CDK6 GS119p5 probe gave a slight cross-hybridization with 3q chromosome. Southern blot analyses were performed with WS2 probe4 and with CDK6 PCR-amplified cDNA probes: E1 (nucleotides 12 to 298; GenBank accession no. X66365), p123, and p45 (nucleotides 446 to 860 and 61817 to 62434, respectively; GenBank accession no. AC002454). Restriction mapping allowed us to locate the breakpoint in patients 1 and 3 inside the breakpoint cluster region previously described within a 3.6 kbp upstream of the transcriptional start site of CDK6.2 As no mitosis was available for FISH analysis in LAN, Igκ light chain locus involvement was confirmed by Southern blot analysis showing the cohybridization of the CDK6 rearranged band with the Igκ probe (Jκ).
SB indicates Southern blot; R, rearranged; and NA, not available.