Oncomedicine 2017; 2:88-92. doi:10.7150/oncm.19362 This volume

Research Paper

Coexistence of Two Novel Mutations in CDKN2A and PMS1 Genes in a Single Patient Identifies a New and Severe Cancer Predisposition Syndrome

Marco Cassone1✉, Leila Baghernajad Salehi1, Gianluca Tedaldi2, Michela Tebaldi2, Valentina Zampiga2, Michela Biancolella1, Barbara Testa1, Daniele Calistri2, Gerarda Mastrogiorgio1, Silvia Lanciotti1, Maria Rosaria D'Apice3, Giuseppe Novelli1, Federica Sangiuolo1

1. Department of biomedicine and prevention, University Tor Vergata Rome, Rome, Italy;
2. Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (Forlì-Cesena), Italy;
3. Medical Genetics Laboratory, Policlinico Tor Vergata, Rome, Italy.

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Cassone M, Salehi LB, Tedaldi G, Tebaldi M, Zampiga V, Biancolella M, Testa B, Calistri D, Mastrogiorgio G, Lanciotti S, D'Apice MR, Novelli G, Sangiuolo F. Coexistence of Two Novel Mutations in CDKN2A and PMS1 Genes in a Single Patient Identifies a New and Severe Cancer Predisposition Syndrome. Oncomedicine 2017; 2:88-92. doi:10.7150/oncm.19362. Available from http://www.oncm.org/v02p0088.htm

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Introduction: Up to 10% of cancers occur through the inherited mutation of a group of genes called cancer predisposition genes [1]. Carriers of monoallelic mutations of these genes are associated with an increased susceptibility to cancer. Autosomal dominant cancer predisposition genes for common cancers have been well recognized for over decade. Each newly identified cancer predisposition gene has been associated with a distinctive autosomal dominant or recessive cancer syndrome [2]. The CDKN2A is the major known melanoma susceptibility gene and has been associated with Familial atypical multiple mole melanoma syndrome (FAMMM #155601), while PMS1 gene is involved in mismatch repair (MMR) process and its mutations have been associated with Lynch syndrome (LS) (HNPCC for hereditary non polyposis colorectal cancers) (OMIM #120435) in few cases [3].

Materials and methods: Genetic counseling, molecular analysis of 94 genes by using ''IlluminaTruSight Cancer'' panel.

Results: We have detected in a patient with a novel frameshift mutation within PMS1 gene, PMS1c.1139dupA p.Y380_S381delinsX, and in the same time a novel mutation within CDKN2a gene, CDKN2a c.58delG p.V20X. In this way, the coexistence of two germline mutations in two different genes, already associated to cancer predisposition syndrome, such as LS and FAMMM have been described.

Discussion: Our data frame this case as a new and severe cancer predisposition syndrome. An appropriate genetic counseling surely represents the key step for a correct test choice in panel genes era.

Keywords: PMS1, CDKN2A, Lynch syndrome, cancer predisposition syndrome, familial melanoma.