(A) Karyotype of
E-MycCdk4+/+ lymphoma.
Trisomy of chr 6 and/or chr 5 was evident in most lymphomas.
(B) Abnormal karyotypes are a hallmark of
Eμ-MycCdk4–/–
lymphomas, including deletions of chr 6 at region C2, translocation of chr 6
and chr 12 with breakpoints (6;12)(C2;F1), trisomy of chr 18, loss of chr X,
deletions of chr 3 and chr 16 at regions F2.2 and 16, respectively,
translocation between chr 3 and chr 16, and the der(16) with [+der(3)t(3;16)(F2.2;C2),der(16)t(3;16) (F2.2;C2)ins(16;?)(C2;?)]. Karyotypes shown are
representative of 20 cells for each lymphoma. (C) Statistical
analysis of genomic instability in
Eμ-MycCdk4–/–
versus Eμ-MycCdk4+/+
lymphomas. The numbers of aberrant chromosomes (translocation, partial
genomic loss and gain) per lymphoma are shown for
Eμ-MycCdk4–/–
and Eμ-MycCdk4+/+
lymphomas. Eμ-MycCdk4+/+
lymphomas (n = 6) with 0, 1, 2, and greater than or equal
to 3 aberrant chromosomes are indicated. All
Eμ-MycCdk4–/–
lymphomas (n = 6) had more than 3 aberrant chromosomes
(Supplemental Table 3). (D) FISH analyses of
Eμ-MycCdk4–/–
lymphomas. Metaphase samples of B220+ cells from
Eμ-MycCdk4+/+ and
Eμ-MycCdk4–/–
lymphomas were assessed by FISH with 5′ (green) and 3′ (red)
Igh probes that flank the 2Mb Igh
locus on chr 12 (37). An intact
Igh locus had colocalized red and green signals, while
a broken locus had split red and green signals. FISH analyses confirmed
complex translocations in
Eμ-MycCdk4–/–
lymphomas. Original magnification, ×1,500. Ch, constant (C) region of
Igh locus; Vh, variable (V) region of
Igh locus. (E) Statistical analysis of
translocated versus wild-type Igh loci in
Eμ-MycCdk4–/–
and
Eμ-MycCdk4+/+
lymphomas (n = 6, P < 0.01).