CDK4

WP

Definition: Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. CDK4 is a member of the cyclin-dependent kinase family.

CDK4 forms a complex with cyclin D. The complex phosphorylates RB, allowing the cell to progress through the G1 restriction point.

Pathology

 amplification and/or overexpression in tumors

• liposarcomas (16160477)
  • atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) (16160477)
  • dedifferentiated liposarcoma (DDLPS) (16160477)

 mutations in tumors

• pulmonary carcinoma (lung cancer)
• CDK4-associated melanoma (16419059)

Immunochemistry

 The combination of MDM2 or CDK4 shows 100% sensitivity and 97.5% specificity for the diagnosis of low-grade osteosarcoma. (20601938)

• MDM2 and CDK4 immunostains therefore reliably distinguish low-grade osteosarcoma from benign histological mimics, and their combination may serve as a useful adjunct in this difficult differential diagnosis. (20601938)
• Parosteal osteosarcoma and low-grade central osteosarcoma are two types of low-grade osteosarcoma that show similar clinical behaviors, histological features, and genetic background (ie, amplified sequences of 12q13-15, including MDM2 and CDK4).
• Low-grade osteosarcoma is often confused with benign lesions.

Inhibitors

 palbociclib

See also

 P16(INK4A)-CDK4/6-RB pathway
 12q13 amplification

References

 Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics. Yoshida A, Ushiku T, Motoi T, Shibata T, Beppu Y, Fukayama M, Tsuda H. Mod Pathol. 2010 Jul 2. PMID: 20601938

 Sirvent N, Coindre JM, Maire G, Hostein I, Keslair F, Guillou L, Ranchere-Vince D, Terrier P, Pedeutour F. Detection of MDM2-CDK4 Amplification by Fluorescence In Situ Hybridization in 200 Paraffin-embedded Tumor Samples: Utility in Diagnosing Adipocytic Lesions and Comparison With Immunohistochemistry and Real-time PCR. Am J Surg Pathol. 2007 Oct;31(10):1476-1489. PMID: 17895748

 Shimada S, Ishizawa T, Ishizawa K, Matsumura T, Hasegawa T, Hirose T. The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers. Hum Pathol. 2006 Sep;37(9):1123-9. PMID: 16938516

 Muthusamy V, Hobbs C, Nogueira C, Cordon-Cardo C, McKee PH, Chin L, Bosenberg MW. Amplification of CDK4 and MDM2 in malignant melanoma. Genes Chromosomes Cancer. 2006 May;45(5):447-54. PMID: 16419059