Figure 4
Figure 4. Inactivation of INK4c/P18 in MCL. (A) Array CGH studies and further screen with genomic PCR identified homozygous deletion of INK4c/P18 in 2 MCL cell lines (UPN1 and HBL2) but not in the remaining B-NHL cell lines. (B) Affymetrix oligonucleotide microarrays performed in MCL cell lines of genes located in 1p36-1p32.3 showed absence of CDKN2C expression in both cell lines. (C) Mutation screening identified hemizygous loss and point mutation of INK4c/P18 at a critical splicing site of the remaining allele in JEKO1 cell line, which correlated with absence of P18 expression. (D) Western blot analysis revealed absence of protein expression in these 3 cell lines (UPN1, HBL2, and JEKO1) but also in the majority of other MCL cell lines (JVM2, IRM2) and in patients with MCL (in the figure, lymph node biopsies from patients P1213, P1003, and P7345), whereas INK4c/P18 protein expression was observed in the majority of other B-NHL subtypes. (E) IHC on tissue microarrays revealed absence of expression of INK4c/P18 in MCL with IGH unmutated status.

Inactivation of INK4c/P18 in MCL. (A) Array CGH studies and further screen with genomic PCR identified homozygous deletion of INK4c/P18 in 2 MCL cell lines (UPN1 and HBL2) but not in the remaining B-NHL cell lines. (B) Affymetrix oligonucleotide microarrays performed in MCL cell lines of genes located in 1p36-1p32.3 showed absence of CDKN2C expression in both cell lines. (C) Mutation screening identified hemizygous loss and point mutation of INK4c/P18 at a critical splicing site of the remaining allele in JEKO1 cell line, which correlated with absence of P18 expression. (D) Western blot analysis revealed absence of protein expression in these 3 cell lines (UPN1, HBL2, and JEKO1) but also in the majority of other MCL cell lines (JVM2, IRM2) and in patients with MCL (in the figure, lymph node biopsies from patients P1213, P1003, and P7345), whereas INK4c/P18 protein expression was observed in the majority of other B-NHL subtypes. (E) IHC on tissue microarrays revealed absence of expression of INK4c/P18 in MCL with IGH unmutated status.

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