Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.
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PMID:Germline mutations in BAP1 predispose to melanocytic tumors. 2187 3

BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions.
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PMID:BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations. 2547 27

Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.
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PMID:Uveal melanoma: relatively rare but deadly cancer. 2791 50

A healthy 31-year-old female presented with an elevated vascular lesion on the right lower eyelid margin. Histology results from excisional biopsy demonstrated a range of intradermally nested atypical melanocytes with negative staining for BRCA1-associated protein 1, confirming the diagnosis of Wiesner nevus. Wiesner nevi may be a cutaneous hallmark of the BRCA1-associated protein 1-associated cancer susceptibility syndrome, and to our knowledge, this is the first report of such a lesion presenting anywhere on the ocular adnexa.
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PMID:Wiesner Nevus of the Eyelid. 2870 Apr 1

BRCA1-associated protein 1(BAP1) inactivated melanocytic nevi are pink to tan and dome-shaped in clinical appearance, resembling dermal nevi, but with distinct histologic features of two melanocytic subpopulations: larger atypical melanocytes and nests of smaller, blander nevoid melanocytes. Pedigrees with BAP1 mutations are at greater risk of various malignancies. We report the case of a 16-year-old boy with multiple benign-appearing nevi, all demonstrating loss of BAP1 on immunohistochemistry. History revealed that his father had died of paraganglioma, which is also associated with BAP1 mutations.
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PMID:Germline BRCA1-associated protein 1 mutation presenting as BAP1 inactivated melanocytic nevi in a child of a father with fatal paraganglioma. 2997 97

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene, located on chromosome 3p21, encoding BAP1 nuclear protein, which is associated with a subset of melanocytic tumors with distinct cytologic features. Single nucleotide polymorphism array (SNP-array) is a molecular karyotyping technique that can detect copy number variations and loss of heterozygosity in various fresh and formalin-fixed paraffin-embedded tissues. Herein we present a 56-year-old female, who presented with a lesion on her left nose/cheek that was growing in size and changing in color. Histopathology was characteristic of a BAP1-deficient melanocytic neoplasm, with a biphasic population of cytologically bland conventional nevomelanocytes and a proliferation of large epithelioid melanocytes with abundant eosinophilic cytoplasm. Immunohistochemistry for BAP1 showed loss of nuclear labeling in the epithelioid melanocytes. SNP-array revealed a chromosome 21q22.1 monoaberration with no chromosome 3 abnormalities. The detection of this aberration prompted a discussion as to whether the lesion was best designated as a nevus or tumor. SNP-array on the patient's blood showed the same monoaberration of chromosome 21q22.1. This case emphasizes the importance of interpreting microarray results in the context of morphology, as germline aberrations can be a pitfall when assessing the genomic stability of a melanocytic proliferation by SNP array.
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PMID:BAP1-deficient tumor/nevus with germline aberration: A potential pitfall in assessing melanocytic neoplasms with single nucleotide polymorphism array. 3105 49

Germline mutations in BRCA1-associated protein 1 (BAP1) are associated with several neoplasms, including BAP1-inactivated melanocytic tumors (BIMTs). BIMTs are classically described as biphenotypic melanocytic proliferations with BAP1-deficient large epithelioid and rhabdoid melanocytes showing various degrees of cytologic atypia. This morphology has been traditionally classified as "spitzoid" despite the various differences between these lesions and the more classic Spitz nevi. Herein, we report a case of an otherwise healthy 11-year-old female patient with a family history of several malignancies who presented with multiple pink to brown papules. Histologic and immunohistochemical evaluation identified three lesions with loss of nuclear BAP1 staining. The histologic spectrum of these lesions included junctional spitzoid cells within a triphenotypic proliferation and a separate lesion composed entirely of dermal small to medium-sized epithelioid melanocytes with maturation. BAP1 gene sequencing revealed a germline frameshift pathogenic BAP1 mutation, denoted c.1717delC. This case provides further evidence that not all BIMTs conform to classic morphological criteria and that the morphologic spectrum includes lesions resembling conventional nevi. As BIMTs can serve as an early marker of the BAP1 hereditary tumor predisposition syndrome, we believe a need exists for a more comprehensive combined clinical and pathological approach for BIMT identification.
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PMID:The morphologic spectrum of germline-mutated BAP1-inactivated melanocytic tumors includes lesions with conventional nevic melanocytes: A case report and review of literature. 3120 29