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CDK4 Gene Amplification

MedGen UID:
1371121
•Concept ID:
C4329591
•
Cell or Molecular Dysfunction
Synonyms: CDK4 Amplification; Cell Division Kinase 4 Gene Amplification; Cyclin Dependent Kinase 4 Gene Amplification

Definition

A molecular genetic abnormality indicating the presence of multiple copies of the CDK4 gene. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCDK4 Gene Amplification

Professional guidelines

PubMed

New treatment options for hormone receptor positive breast cancer in 2023.
Lüftner D
Curr Opin Obstet Gynecol 2023 Feb 1;35(1):62-66. Epub 2022 Nov 7 doi: 10.1097/GCO.0000000000000834. PMID: 36341983
Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response.
Hong JY, Cho HJ, Yun KH, Lee YH, Kim SH, Baek W, Kim SK, Lee Y, Choi YL, Kwon M, Kim HS, Lee J
Cancer Res Treat 2023 Apr;55(2):671-683. Epub 2022 Sep 27 doi: 10.4143/crt.2022.251. PMID: 36164943Free PMC Article
Cyclin D degradation by E3 ligases in cancer progression and treatment.
Qie S, Diehl JA
Semin Cancer Biol 2020 Dec;67(Pt 2):159-170. Epub 2020 Jan 30 doi: 10.1016/j.semcancer.2020.01.012. PMID: 32006569Free PMC Article

Recent clinical studies

Etiology

High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.
Ricciotti RW, Baraff AJ, Jour G, Kyriss M, Wu Y, Liu Y, Li SC, Hoch B, Liu YJ
Cancer Genet 2017 Dec;218-219:69-80. Epub 2017 Sep 22 doi: 10.1016/j.cancergen.2017.09.005. PMID: 29153098
Lipoleiomyosarcoma of the larynx.
Trijolet JP, Lescanne E, Morinière S, Robier A, Bakhos D
Head Neck 2013 May;35(5):E164-6. Epub 2012 Feb 6 doi: 10.1002/hed.22905. PMID: 22307930
MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype.
Yoshida A, Ushiku T, Motoi T, Beppu Y, Fukayama M, Tsuda H, Shibata T
Am J Surg Pathol 2012 Mar;36(3):423-31. doi: 10.1097/PAS.0b013e31824230d0. PMID: 22301501
Molecular genetic analysis of giant cell glioblastomas.
Meyer-Puttlitz B, Hayashi Y, Waha A, Rollbrocker B, Boström J, Wiestler OD, Louis DN, Reifenberger G, von Deimling A
Am J Pathol 1997 Sep;151(3):853-7. PMID: 9284834Free PMC Article
MDM2 and CDK4 gene amplification in Ewing's sarcoma.
Ladanyi M, Lewis R, Jhanwar SC, Gerald W, Huvos AG, Healey JH
J Pathol 1995 Feb;175(2):211-7. doi: 10.1002/path.1711750209. PMID: 7738717

Diagnosis

Rare myxoid pleomorphic liposarcoma: a case report and literature review.
Shen Y, Zhao L, Li A, Peng Q, Liu Q, Wang L, Liu Z
J Clin Pathol 2024 Apr 18;77(5):358-362. doi: 10.1136/jcp-2023-209223. PMID: 38123348
MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype.
Yoshida A, Ushiku T, Motoi T, Beppu Y, Fukayama M, Tsuda H, Shibata T
Am J Surg Pathol 2012 Mar;36(3):423-31. doi: 10.1097/PAS.0b013e31824230d0. PMID: 22301501
Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: a potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas.
Hostein I, Pelmus M, Aurias A, Pedeutour F, Mathoulin-Pélissier S, Coindre JM
J Pathol 2004 Jan;202(1):95-102. doi: 10.1002/path.1495. PMID: 14694526
CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons.
Wei G, Lonardo F, Ueda T, Kim T, Huvos AG, Healey JH, Ladanyi M
Int J Cancer 1999 Jan 18;80(2):199-204. doi: 10.1002/(sici)1097-0215(19990118)80:2<199::aid-ijc7>3.0.co;2-4. PMID: 9935200
MDM2 and CDK4 gene amplification in Ewing's sarcoma.
Ladanyi M, Lewis R, Jhanwar SC, Gerald W, Huvos AG, Healey JH
J Pathol 1995 Feb;175(2):211-7. doi: 10.1002/path.1711750209. PMID: 7738717

Therapy

Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down-regulation.
Zuco V, Pasquali S, Tortoreto M, Brich S, Percio S, Dagrada GP, Colombo C, Sanfilippo R, Lauricella C, Gounder M, El Bezawy R, Barisella M, Dei Tos AP, Casali PG, Gronchi A, Stacchiotti S, Zaffaroni N
J Exp Clin Cancer Res 2021 Mar 1;40(1):83. doi: 10.1186/s13046-021-01886-x. PMID: 33648535Free PMC Article
CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons.
Wei G, Lonardo F, Ueda T, Kim T, Huvos AG, Healey JH, Ladanyi M
Int J Cancer 1999 Jan 18;80(2):199-204. doi: 10.1002/(sici)1097-0215(19990118)80:2<199::aid-ijc7>3.0.co;2-4. PMID: 9935200

Prognosis

High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.
Ricciotti RW, Baraff AJ, Jour G, Kyriss M, Wu Y, Liu Y, Li SC, Hoch B, Liu YJ
Cancer Genet 2017 Dec;218-219:69-80. Epub 2017 Sep 22 doi: 10.1016/j.cancergen.2017.09.005. PMID: 29153098
MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.
Wong DD, Low IC, Peverall J, Robbins PD, Spagnolo DV, Nairn R, Carey-Smith RL, Wood D
Pathology 2016 Apr;48(3):203-9. Epub 2016 Mar 2 doi: 10.1016/j.pathol.2016.02.007. PMID: 27020493
CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.
Lee S, Park H, Ha SY, Paik KY, Lee SE, Kim JM, Park JB, Kwon CH, Joh JW, Choi YL, Kim SJ
PLoS One 2014;9(8):e99452. Epub 2014 Aug 14 doi: 10.1371/journal.pone.0099452. PMID: 25121597Free PMC Article
MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype.
Yoshida A, Ushiku T, Motoi T, Beppu Y, Fukayama M, Tsuda H, Shibata T
Am J Surg Pathol 2012 Mar;36(3):423-31. doi: 10.1097/PAS.0b013e31824230d0. PMID: 22301501
Molecular genetic analysis of giant cell glioblastomas.
Meyer-Puttlitz B, Hayashi Y, Waha A, Rollbrocker B, Boström J, Wiestler OD, Louis DN, Reifenberger G, von Deimling A
Am J Pathol 1997 Sep;151(3):853-7. PMID: 9284834Free PMC Article

Clinical prediction guides

Rare myxoid pleomorphic liposarcoma: a case report and literature review.
Shen Y, Zhao L, Li A, Peng Q, Liu Q, Wang L, Liu Z
J Clin Pathol 2024 Apr 18;77(5):358-362. doi: 10.1136/jcp-2023-209223. PMID: 38123348
High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.
Ricciotti RW, Baraff AJ, Jour G, Kyriss M, Wu Y, Liu Y, Li SC, Hoch B, Liu YJ
Cancer Genet 2017 Dec;218-219:69-80. Epub 2017 Sep 22 doi: 10.1016/j.cancergen.2017.09.005. PMID: 29153098
MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.
Wong DD, Low IC, Peverall J, Robbins PD, Spagnolo DV, Nairn R, Carey-Smith RL, Wood D
Pathology 2016 Apr;48(3):203-9. Epub 2016 Mar 2 doi: 10.1016/j.pathol.2016.02.007. PMID: 27020493
CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.
Lee S, Park H, Ha SY, Paik KY, Lee SE, Kim JM, Park JB, Kwon CH, Joh JW, Choi YL, Kim SJ
PLoS One 2014;9(8):e99452. Epub 2014 Aug 14 doi: 10.1371/journal.pone.0099452. PMID: 25121597Free PMC Article
MDM2 and CDK4 gene amplification in Ewing's sarcoma.
Ladanyi M, Lewis R, Jhanwar SC, Gerald W, Huvos AG, Healey JH
J Pathol 1995 Feb;175(2):211-7. doi: 10.1002/path.1711750209. PMID: 7738717

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