Article Text
Abstract
Familial atypical multiple mole melanoma syndrome (FAMMM) is characterised by dysplastic naevi, malignant melanoma and pancreatic cancer. Given that large deletions involving CDKN2A (cyclin-dependent kinase inhibitor 2A) account for only 2% of cases, we describe a family that highlights the co-occurrence of both melanoma and neural system tumours to aid clinical recognition and propose a management strategy. A patient with multiple neurofibromas was referred with a provisional diagnosis of neurofibromatosis type 1 (NF1). Prior molecular testing, though, had failed to identify an NF1 mutation by sequencing and multiplex ligation-dependent probe amplification. His family history was significant for multiple in situ/malignant melanomas at young ages and several different cancers reminiscent of an underlying syndrome. A search of the Familial Cancer Database, FaCD Online, highlighted several families with cutaneous melanoma and nervous system tumours who were subsequently identified to have large deletions spanning CDKN2A. Although sequencing of CDKN2A and TP53 failed to identify a mutation, a heterozygous CDKN2A deletion was identified by targeted array comparative genomic hybridisation (CGH). Whole-genome oligonucleotide array CGH and SNP analysis identified an interstitial deletion of at least 1.5 Mb within 9p21.3 and spanning approximately 25 genes. Identification of the underlying molecular abnormality permits predictive testing for at-risk relatives. Given the young cancer diagnoses, a surveillance regimen was developed and a clinical team organised for ongoing management so that genetic testing could be offered to both adults and minor children. Surveillance recommendations addressed cancer risks associated with FAMMM, and other cancers exhibited by this family with a large contiguous gene deletion.
- Cancer: CNS
- Cancer: dermatological
- Clinical genetics
- Genetic screening/counselling
- Molecular genetics
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Footnotes
Contributors Genetic counselling and coordination of genetic testing: MJB. Ongoing medical management: PLG, KSH, HM, MJG and JJD. Drafting and critical revision of the manuscript: MJB, AMG, PLG, KSH, HM, MJG and JJD. All authors read and approved the final manuscript. KSH provided images of array CGH data.
Funding This work was supported in part by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG).
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.