Selection criteria for genetic assessment of patients with familial melanoma

Leachman, Sancy A.; Carucci, John A.; Kohlmann, Wendy; Banks, Kimberly C.; Asgari, Maryam M.; Bergman, Wilma; Bianchi‐Scarrǎ, Giovanna; Brentnall, Teresa A.; Paillerets, Brigitte Bressac-de; Bruno, William; Curiel‐Lewandrowski, Clara; Snoo, Femke A. de; Dębniak, Tadeusz; Demierre, Marie‐France; Elder, David E.; Goldstein, Alisa M.; Grant‐Kels, Jane M.; Halpern, Allan C.; Ingvar, Christian; Kefford, Richard; Lang, Julie; MacKie, Rona M.; Mann, Graham J.; Mueller, Kurt; Newton-Bishop, Julia; Olsson, Håkan; Petersen, Gloria M.; Puig, Susana; Rigel, Darrell S.; Swetter, Susan M.; Tucker, Margaret A.; Yakobson, Emanuel; Zitelli, John A.; Tsao, Hensin

doi:10.1016/j.jaad.2009.03.016

Cited by 166 publications

(164 citation statements)

References 86 publications

Supporting

Mentioning

159

Contrasting

Order By: Relevance

“…Published recommendations for CDKN2A screening include patients with multiple (Z3) primary melanomas, or families with at least one melanoma and two other instances of melanoma or pancreatic cancer in the family, with mutation detection rates of 20-40% in this setting. [36][37][38] Under these recommendations, two of the seven (29%) families meeting criteria were determined to carry a mutation in this study, and we believe this is a reasonable proportion for discriminating candidates for genetic testing. However, it should also be noted that the majority of mutations would not have been identified with this approach.…”

Section: Discussionmentioning

confidence: 89%

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

et al. 2010

View full text Add to dashboard Cite

Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups. Penetrance and likelihood of carrying mutations by family history were estimated. Among 1537 cases, 9 (0.6%) carried germline mutations in CDKN2A, including three previously unreported mutations. CDKN2A mutation carriers were more likely to have a family history of pancreatic cancer (P¼0.003) or melanoma (P¼0.03), and a personal history of melanoma (P¼0.01). Among cases who reported having a first-degree relative with pancreatic cancer or melanoma, the carrier proportions were 3.3 and 5.3%, respectively. Penetrance for mutation carriers by age 80 was calculated to be 58% for pancreatic cancer (95% confidence interval (CI) 8-86%), and 39% for melanoma (95% CI 0-80). Among cases who ever smoked cigarettes, the risk for pancreatic cancer was higher for carriers compared with non-carriers (HR 25.8, P¼2.1Â10 À13 ), but among nonsmokers, this comparison did not reach statistical significance. Germline mutations in CDKN2A among unselected pancreatic cancer patients are uncommon, although notably penetrant, especially among smokers. Carriers of germline mutations of CDKN2A should be counseled to avoid tobacco use to decrease risk of pancreatic cancer in addition to taking measures to decrease melanoma risk. Keywords: cyclin-dependent kinase inhibitor p16; genes; p16; pancreatic neoplasms INTRODUCTION Pancreatic cancer is associated with very poor survival rates, with long-term survivors limited to those with resected early stage tumors. However, detection of pancreatic cancer at an early stage is challenging, and this mandates identification of high-risk groups to be targeted for prevention and screening intervention.Since first observed by Lynch and Krush in 1968, 1 the incidence of pancreatic cancer has been noted to be increased in many families affected by inherited melanoma syndromes. In genetic analyses of these families, 20-40% of inherited increased melanoma susceptibility can be linked to mutations of the CDKN2A gene (p16/Ink4) located on chromosome 9p21. [2][3][4][5] As a result of the increased incidence of pancreatic cancer in melanoma families with CDKN2A mutations, it was hypothesized that mutations likely also predispose to pancreatic cancer development. 2 Mutations in CDKN2A have subsequently been described in familial pancreatic cancer kindreds, some without melanoma. 3,4 Somatic mutations of CDKN2A are present in up to 95% of pancreatic tumors. 5 These findings provide further support for the premise that CDKN2A mutations have an important role in the development of pancreatic cancer. Clinical findings in mutation carri...

show abstract

Section: Discussionmentioning

confidence: 89%

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Unsurprisingly, a positive family history is a strong risk factor for the evolution of this disease. As the number of first-degree relatives with melanoma increases, so does the risk of developing the disease (6). Patients with one firstdegree relative with melanoma are 1.7 times more likely to be diagnosed with melanoma, whereas two first-degree relatives incur a nine-fold increase in risk.…”

Section: General Risk Factorsmentioning

confidence: 99%

“…Such immunosuppression may be the result of an existing neoplastic condition. For example, approximately 5% of patients with a personal history of melanoma will be diagnosed with a second melanoma (6). In addition, patients with a personal history of nonmelanoma skin cancer have more than a fourfold relative risk of developing melanoma.…”

Section: General Risk Factorsmentioning

confidence: 99%

“…XP, an autosomal recessive condition in which UV-related DNA repair mechanisms are deficient, carries an approximately 1000-fold increase in the risk of melanoma. Sun avoidance and regular self-skin examinations are mandatory, as is frequent surveillance by a dermatologist with extensive XP experience (6,7).…”

Section: Populations At Increased Riskmentioning

confidence: 99%

“…FAMMM syndrome, also known as the B-K mole syndrome, is caused by germline mutations in CDKN2A (6). An autosomal dominant condition, FAMMM syndrome has incomplete penetrance.…”

Section: Populations At Increased Riskmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Presentation and Staging of Melanoma

Ward

Lambreton

Goel

et al. 2017

Cutaneous Melanoma: Etiology and Therapy

101

View full text Add to dashboard Cite

Cutaneous melanoma is responsible for the vast majority of skin cancer-related deaths in the United States. Known risk factors include genetic defects, environmental exposures, and a combination of both. Among environmental risks, exposure to ultraviolet rays is the most important and the most modifiable risk factor. Several genetic syndromes involve increased risk of melanoma, including xeroderma pigmentosum, familial atypical multiple moles and melanoma syndrome, BRCA2 mutation, and congenital melanocytic nevi. Although the necessity of implementation remains controversial, the most effective melanoma screening technique is the whole-body skin examination. Typically, melanoma lesions are incidentally discovered during routine skin examination using the "ABCDE" mnemonic. Once suspected, questions pertaining to the sites of potential metastasis should be asked and excisional or partial biopsy should be considered. The primary histologic subtypes of melanoma include superficial spreading, lentigo maligna, nodular, acral lentiginous, desmoplastic, and amelanotic. Melanoma staging is completed via clinical and histologic assessment using the American Joint Committee on Cancer TNM system. Delayed or deficient elements of initial melanoma evaluation can limit patient outcomes and increase disease-related mortality. Clinicians involved in the diagnosis or treatment of cutaneous melanoma must be familiar with the available screening options, key steps of diagnosis, and the staging ramifications of disease discovery.

show abstract

Prevalence ofMITFp.E318K in Patients With Melanoma Independent of the Presence ofCDKN2ACausative Mutations

et al. 2016

Self Cite

View full text Add to dashboard Cite

The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers. OBJECTIVES To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features. DESIGN, SETTING, AND PARTICIPANTS A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p.E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age-and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls.

show abstract

Selection criteria for genetic assessment of patients with familial melanoma

Cited by 166 publications

References 86 publications

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

Clinical Presentation and Staging of Melanoma

Prevalence ofMITFp.E318K in Patients With Melanoma Independent of the Presence ofCDKN2ACausative Mutations

Contact Info

Product

Resources

About