CDKN2A (p14ARF) and CDK4 Gene Mutations

Melanoma Cancer Syndrome (MCS)

CDKN2A ASSOCIATED CANCER RISKS

 BREASTOVARIANGASTRICCOLORECTALPANCREATICMELANOMAPROSTATEENDOMETRIALOTHER

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Additional Information

CDKN2A (p14ARF) gene

Associated Syndrome Name: Melanoma Cancer Syndrome (MCS)

CDKN2A (p14ARF) Summary Cancer Risk Table

Cancer Genetic Cancer Risk
MelanomaHigh Risk
PancreaticElevated Risk

CDKN2A (p14ARF) gene Overview

Melanoma Cancer Syndrome (MCS) 1, 2, 3, 4
  • Individuals with CDKN2A (p14ARF) mutations have Melanoma Cancer Syndrome (MCS).
  • Patients with MCS have a high risk of developing melanoma. There are currently no exact estimates of the risk associated with CDKN2A (p14ARF) mutations, but it is believed that melanoma risks are similar to those for patients with a similar condition due to mutations in the CDKN2A (p16INK4a) gene. Those risks are provided below. It is possible that these estimates will change over time as we learn more about the exact risks associated with mutations in CDKN2A (p14ARF).
  • Patients with MCS due to mutations in CDKN2A (p14ARF) may also have a high risk for pancreatic cancer, as a high risk for pancreatic cancer has been observed in some families with mutations in the related gene CDKN2A (p16INK4a). Concern about pancreatic cancer risk should be higher for patients who have a family history of this cancer.
  • Although there is a high risk for melanoma, and possibly pancreatic cancer, in patients with MCS, it may be possible to reduce this risk with appropriate medical management, including increased attention to surveillance and lifestyle modifications. Guidelines from expert groups for the management of patients with increased risks for these cancers are listed below. Since information about the cancer risks associated with CDKN2A (p14ARF) mutations is relatively new, and there is uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics professionals who have expertise in this emerging area of knowledge.

CDKN2A (p14ARF) gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
MelanomaTo age 501, 4, 514%-50%0.3%
To age 801, 4, 528%-76%1.6%
PancreaticTo age 752, 3, 5Elevated risk0.7%

CDKN2A (p14ARF) Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
MelanomaEducation about the importance of skin protection, such as sun avoidance, protective clothing and sunscreen.6, 7InfancyOngoing
Whole-body skin examinations conducted by the patient or family member.6, 710 yearsMonthly
Clinical skin examinations by an appropriately trained provider, with consideration of whole-body photography and close-up photography of atypical nevi for ongoing comparison.6, 710 yearsEvery 6 to 12 months
PancreaticConsider available options for pancreatic cancer screening, including endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in screening for pancreatic cancer, preferably within research protocols.8, 9Age 40, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the familyAnnually
Provide education about ways to reduce pancreatic cancer risk, such as not smoking and losing weight.8, 10IndividualizedIndividualized

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the CDKN2A (p14ARF) gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Since there are screening and preventative measures recommended to begin in infancy or early childhood for individuals with CDKN2A (p14ARF) mutations, consideration should be given to the possibility of mutation testing at young ages.

References

  1. Begg CB, et al. Genes Environment and Melanoma Study Group. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J Natl Cancer Inst. 2005 97:1507-15. PMID: 16234564.
  2. Goldstein AM, et al. Melanoma Genetics Consortium (GenoMEL). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006 66:9818-28. PMID: 17047042.
  3. Vasen HF, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000 87:809-11. PMID: 10956390.
  4. Bishop DT, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002 94:894-903. PMID: 12072543.
  5. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
  6. Kefford RF et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999 17:3245-51. PMID: 10506626.
  7. Coit DG et al. NCCN Clinical Practice Guidelines in Oncology®: Melanoma. V 1.2020 Dec 19. Available at http://www.nccn.org.
  8. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
  9. Goggins M, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 69:7-17. PMID: 31672839.
  10. Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology®: Pancreatic Adenocarcinoma. V 1.2020. Nov 26. Available at http://www.nccn.org.
Last Updated on 10-Dec-2020

CDK4 gene

Associated Syndrome Name: Melanoma Cancer Syndrome (MCS)

CDK4 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
MelanomaHigh Risk
PancreaticElevated Risk

CDK4 gene Overview

Melanoma Cancer Syndrome (MCS) 1, 2, 3, 4, 5
  • Individuals with CDK4 mutations have Melanoma Cancer Syndrome (MCS).
  • Patients with MCS have a high risk of developing melanoma. There are currently no exact estimates of the risk associated with CDK4 mutations, but it is believed that melanoma risks are similar to those for patients with a similar condition due to mutations in the CDKN2A (p16INK4a) gene. Those risks are provided below. It is possible that these estimates will change over time as we learn more about the exact risks associated with mutations in CDK4.
  • Patients with MCS due to mutations in CDK4 may also have a high risk for pancreatic cancer, as a high risk for pancreatic cancer has been observed in some families with mutations in the related gene CDKN2A (p16INK4a). Concern about pancreatic cancer risk should be higher for patients who have a family history of this cancer.
  • Although there is a high risk for melanoma, and possibly pancreatic cancer, in patients with MCS, it may be possible to reduce this risk with appropriate medical management, including increased attention to surveillance and lifestyle modifications. Guidelines from expert groups for the management of patients with increased risks for these cancers are listed below. Since information about the cancer risks associated with CDK4 mutations is relatively new, and there is uncertainty about the best ways to reduce these risks, it may be appropriate to interpret these results in consultation with cancer genetics professionals who have expertise in this emerging area of knowledge.

CDK4 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
MelanomaTo age 501, 5, 614%-50%0.3%
To age 801, 5, 628%-76%1.6%
PancreaticTo age 752, 4, 6Elevated risk0.7%

CDK4 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
MelanomaEducation about the importance of skin protection, such as sun avoidance, protective clothing and sunscreen.7, 8InfancyOngoing
Whole-body skin examinations conducted by the patient or family member.7, 810 yearsMonthly
Clinical skin examinations by an appropriately trained provider, with consideration of whole-body photography and close-up photography of atypical nevi for ongoing comparison.7, 810 yearsEvery 6 to 12 months
PancreaticCurrently there are no specific medical management guidelines for pancreatic cancer risk in mutation carriers.NANA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the CDK4 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Since there are screening and preventative measures recommended to begin in infancy or early childhood for individuals with CDK4 mutations, consideration should be given to the possibility of mutation testing at young ages.

References

  1. Begg CB, et al. Genes Environment and Melanoma Study Group. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. J Natl Cancer Inst. 2005 97:1507-15. PMID: 16234564.
  2. Goldstein AM, et al. Melanoma Genetics Consortium (GenoMEL). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006 66:9818-28. PMID: 17047042.
  3. Goldstein AM, et al. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000 92:1006-10. PMID: 10861313.
  4. Vasen HF, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000 87:809-11. PMID: 10956390.
  5. Bishop DT, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002 94:894-903. PMID: 12072543.
  6. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
  7. Kefford RF et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999 17:3245-51. PMID: 10506626.
  8. Coit DG et al. NCCN Clinical Practice Guidelines in Oncology®: Melanoma. V 1.2020 Dec 19. Available at http://www.nccn.org.
Last Updated on 10-Dec-2020