A large de novo9p21.3 deletion in a girl affected by astrocytoma and multiple melanoma

Frigerio, Simona; Disciglio, Vittoria; Manoukian, Siranoush; Peissel, Bernard; Torre, Gabriella Della; Maurichi, Andrea; Collini, Paola; Pasini, Barbara; Gotti, Giacomo; Ferrari, Andrea; Rivoltini, Licia; Massimino, Maura; Rodolfo, Monica

doi:10.1186/1471-2350-15-59

Cited by 19 publications

(20 citation statements)

References 34 publications

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“…Although the contribution of ANRIL expression to neural system tumours remains unknown, SNPs which alter its expression, have been associated with numerous diseases including coronary artery disease, stroke, diabetes as well as melanoma and glioma 36. Most recently, Frigerio et al 37 reported a patient with both astrocytoma and multiple melanomas with the largest constitutive deletion described to date involving 9p21.3 and spanning approximately 2135 Mb. Our proband, reported herein, adds to this growing list of families with large deletions extending beyond CDKN2A , thus raising the question of whether or not this could represent an emerging contiguous gene deletion syndrome.…”

Section: Discussionmentioning

confidence: 99%

An interstitial deletion within 9p21.3 and extending beyondCDKN2Apredisposes to melanoma, neural system tumours and possible haematological malignancies

et al. 2016

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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 ligationdependent 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). Wholegenome 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.

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Section: Discussionmentioning

confidence: 99%

An interstitial deletion within 9p21.3 and extending beyondCDKN2Apredisposes to melanoma, neural system tumours and possible haematological malignancies

et al. 2016

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“…37 Larger scale chromosome 9p21 alterations (including deletions involving the CDKN2A / CDKN2B / CDKN2BAS gene cluster up to the MLLT3 gene) have been described in some isolated cases. 38–41 Kaufman et al described this syndrome in 1993 when they reported concurrent CMMs and multiple types of nervous system tumors (NSTs) in eight members of a family over three generations. 42 Later, Azizi et al reported that 17 individuals with CMM, among 15 families, had one or more additional relatives with tumors of the nervous system.…”

Section: 3 Melanoma-astrocytoma Syndrome (Omim 155755)mentioning

confidence: 99%

“…38–40, 44 A positive association between radiotherapy for the NSTs and the incidence of CMM in these patients has been proposed, but remains unsubstantiated. 41 …”

Section: 3 Melanoma-astrocytoma Syndrome (Omim 155755)mentioning

confidence: 99%

Hereditary melanoma: Update on syndromes and management

Soura

Eliades

Shannon

et al. 2016

Journal of the American Academy of Dermatology

174

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Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis.

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“…Melanomas 190 were all between stages II and V, and were verified by a 191 qualified dermatopathologist. Upon review, melanoma 192 specimens with less than 60% tumor tissue (such as 193 specimens with a brisk lymphocytic infiltrate) were ex-194 cluded from study.…”

mentioning

confidence: 99%

“…CDKN2B is one of the 1047 genes located at 9p21 and has been shown to be 1048 deleted in melanoma [6,192] and other cancers such…”

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confidence: 99%

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

Mahas

Potluri

Kent

et al. 2016

CBM

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Abstract. BACKGROUND: Skin melanocytes can give rise to benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. OBJECTIVE: This substantial difference between melanoma and benign nevi can be exploited to discriminate between melanoma and benign nevi. METHODS: Array-comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA copy number. In this study, high resolution, genome-wide single-nucleotide polymorphism (SNP) arrays were utilized to perform comprehensive and detailed analyses of recurrent copy number aberrations in 41 melanoma samples in comparison with 21 benign nevi. RESULTS: We found statistically significant copy number gains and losses within melanoma samples. Some of the identified aberrations are previously implicated in melanoma. Moreover, novel regions of copy number alterations were identified, revealing new candidate genes potentially involved in melanoma pathogenesis. CONCLUSIONS: Taken together, these findings can help improve melanoma diagnosis and introduce novel melanoma therapeutic targets.Keywords: Array comparative genomic hybridization, melanoma, FFPE highly lethal forms of cancer. Although it accounts 10 for the minority of skin cancers, a large majority 11 (75%) of skin cancer related-deaths are accounted for 12 by melanoma [1,2]. The incidence and mortality of 13 melanoma has increased dramatically in the last few 14 decades [3]. The American Cancer Society estimates 15 that about 73,870 people in United States will be diag-16 nosed with melanoma in 2015 and about 9,940 people 17 are expected to die from the disease. Importantly, the 18 5-year survival rate of melanoma depends on the stage 19 of the disease when it is diagnosed. It can be as high 20 as 98% when the melanoma is detected early before 21 it spreads to the lymph nodes or other organs. When 22 melanoma reaches the lymph nodes, the 5-year sur-23 vival rate drops to 62%, and to 15% when melanoma 24 spread to other organs [2]. Sequences for the primer pairs and cycling parame-286 ters were as follows: 5'-AATCGGGCTG-3' and 5'-287 GAAACGGGTG-3', 94• C for 2.5 minutes, then 45 cy-288 cles of 1 minute 94• C, 1 minute 55 • C and 2 minutes 289 72• C, then 7 minutes 72 • C and holding at 4 • C; or 5 -290 TGTGCCCAGTGAAGACTCAG-3' and 5 -GAGTGA 291 GCGGAGAGGGAACT-3', 45 cycles of 94• C for 1 292 minute, 35• C for 1 minute, and 72• C for 2 minute. 293 PCR products were resolved on 3% TBE agarose plus 294 SYBR Safe dye (Life Technologies). Gels were visu-295 alized with a GE ImageQuant LAS-3000 camera (GE 296 Healthcare Life Sciences, Piscataway, NJ, USA). Microarrays 298DNA copy number analysis was performed by hy-299 bridizing the extracted and qualified gDNA to Affy-300 metrix...

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A large de novo9p21.3 deletion in a girl affected by astrocytoma and multiple melanoma

Cited by 19 publications

References 34 publications

An interstitial deletion within 9p21.3 and extending beyondCDKN2Apredisposes to melanoma, neural system tumours and possible haematological malignancies

An interstitial deletion within 9p21.3 and extending beyondCDKN2Apredisposes to melanoma, neural system tumours and possible haematological malignancies

Hereditary melanoma: Update on syndromes and management

Copy number variation in archival melanoma biopsies versus benign melanocytic lesions

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