FISH analysis using dual color probes for the CDKN2C
gene at 1p32.3 and CKS1B gene at 1q21.3 confirmed three copies of 1q in 5.5% of bone marrow cells.
Boikos et al., "The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C
mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes," Clinical Genetics, vol.
Based on their structure and CDK specificity, CDKIs are classified into the INK4 family CDKIs ([p16.sup.INK4a] (Cdkn2a), [p15.sup.INK4b] (Cdkn2b), [p18.sup.INK4c] (Cdkn2c
), and [p19.sup.INK4d] (Cdkn2d)) that inhibit CDK4/6 activity by competing with cyclin D to bind CDK4/6 and the Cip/Kip family CDKIs ([p21.sup.Cip1] (Cdkn1a), [p27.sup.Kip1] (Cdkn1b), and [p57.sup.Kip2] (Cdkn1c)) that associate with both cyclins and CDKs and interfere with the activities of cyclin D-, E-, A-, and B-CDK complexes.
However effects on expression of 5 other genes, CDKN2C
, FHL1, HGF, IL1RL1, CD53, are associated with tumor growth and carcinogenesis.
1p32.3 may also be hemi- and homozygously deleted and contains the two target genes, FAF1 and CDKN2C. CDKN2C is a cyclin-dependent kinase 4 inhibitor involved in negative regulation of the cell cycle, whereas FAF1 encodes a protein involved in initiation and/or enhancement of apoptosis through the Fas pathway.
For example, the downregulation of CDKN2C through del(1p), or the inactivation of CDKN2A via DNA methylation changes may both deregulate the [G.sub.1]/S transition as these genes encode cyclin-dependent kinase inhibitors [65, 103].
For instance, mutations in the HRAS  (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) gene and structural rearrangements affecting the CDKN2C [cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)] gene were identified in the melanoma patient of the aforementioned study.
 Human genes: HRAS, v-Ha-ras Harvey rat sarcoma viral oncogene homolog; CDKN2C, cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4); NRAS, neuroblastoma RAS viral (v-ras) oncogene homolog; CDK8, cyclin-dependent kinase 8; KRAS, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; BRAF, v-raf murine sarcoma viral oncogene homolog B1.
Gene variants of TXN, CDKN2C
, GSTM3, PTH1R, CKB, AOC1, AOC3, TIMP1, and PTN have been identified as other additional genes associated with defense response and inflammatory response in the pathogenesis of DPN (Figure 2) .
Triptolide downregulated the cell cycle-related genes E2F2 E2F3, E2F5, CDKN2C
, CDK7, CDC23, and SMAD3; the MAPK signaling pathway genes FOS, CASP3, JUND, KRAS, MAP2K2; and the Wnt signaling pathway genes WNT4, MYC, and AXIN2.
(78) Among genes overexpressed in MM, several were involved in cell cycle checkpoints, such as CDK1/CDC2 (cyclin-dependent kinase 1), CDC6 (cell division cycle 6, a regulator of replication), CDKN2C
(cyclin-dependent kinase inhibitor 2C, p18), CCNH (cyclin H), CCNB1 (cyclin B1, controlling the cell cycle at the G2/ M transition), CHEK1 (Chk1 is required for checkpoint-mediated cell cycle arrest in response to DNA damage), and FOXM1 (forkhead transcription factor, a regulator of gene expression in the G2 phase).
Identification of 2 distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C
gene from 1 p32 in oligodendroglial tumors.