DNA copy number changes correlate with clinical behavior in melanocytic neoplasms: proposal of an algorithmic approach

Alomari, Ahmed K.; Miedema, Jayson; Carter, Michael D.; Harms, Paul W.; Lowe, Lori; Durham, Alison B.; Fullen, Douglas R.; Patel, Rajiv M.; Hristov, Alexandra C.; Chan, May P.; Wang, Min; Andea, Aleodor A.

doi:10.1038/s41379-020-0499-y

Cited by 23 publications

(30 citation statements)

References 28 publications

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“…12,[36][37][38][39][40] CGH leverages the genome instability typical of melanomas and surveys the entire genome for copy number abnormalities that correlate with clinical behavior. 41,42 Extraction of adequate DNA from small biopsies or shave biopsies can be challenging. However, microarray technologies have significantly decreased specimen requirements, needing only 37 ng DNA.…”

Section: Melanoma Diagnostic Testing Technologiesmentioning

confidence: 99%

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

et al. 2021

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Background: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS). Methods: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model. Results:We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. Conclusion:This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.

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Section: Melanoma Diagnostic Testing Technologiesmentioning

confidence: 99%

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

et al. 2021

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“…Several CNV cut-offs for malignancy have previously been suggested. Based on their case series, Maize et al and Chan et al suggested a cut-off of ≥3 CNVs and ≥4 CNVs, respectively, and Alomari et al proposed an algorithm using ≥4 significant CNVs with additional caveats in case of ≤3 CNVs [16,21,34]. Our current meta-analysis integrates and expands their data, providing more robust evidence for various cut-offs in the classification of intermediate lesions.…”

Section: Discussionmentioning

confidence: 68%

“…Of note, a minority of melanomas did not harbor CNVs, and benign lesions might carry CNVs with limited prognostic value. In contrast, specific CNVs may also be relevant if present in isolation, such as homozygous loss of 9p21 (CDKN2A) [16]. Therefore, CNVs should always be interpreted considering the clinicopathological context.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis

et al. 2021

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Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0–2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0–1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4–11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% CI 0.86–0.94, p<0.001). Two CNV cut-off points demonstrated a sensitivity and specificity higher than 80%. A cut-off of ≥3 CNVs corresponded to 85% sensitivity and 84% specificity, and a cut-off of ≥4 CNVs corresponded to 81% sensitivity and 91% specificity, respectively. This individual patient data meta-analysis provides a comprehensive overview of CNVs in cutaneous intermediate melanocytic lesions, based on the largest pooled cohort of ambiguous melanocytic neoplasms to date. Our meta-analysis suggests that a cut-off of ≥3 CNVs might represent the optimal trade-off between sensitivity and specificity in clinical practice to differentiate intermediate lesions from melanoma.

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“…A recent study by Alomari et al . found that the average number of CNAs increases from 0 in nevi to 0.6 (range 0–3) in atypical nevi to 2.8 (range 0–17) in borderline lesions and to 18.1 (range 0–61) in melanoma 51 . The authors proposed that a SNP‐array test showing 3 or less CNAs should be interpreted as reassuring for a low‐risk melanocytic lesion.…”

Section: Genetics Of Melanocytic Tumorsmentioning

confidence: 99%

“…Conversely, a CGH/SNP array with 4 or more CNAs is worrisome for a high‐risk melanocytic lesion (Figure 4). Again, exceptions are noted as proliferative nodules may show multiple gains and/or losses of entire chromosomes 51 …”

Section: Genetics Of Melanocytic Tumorsmentioning

confidence: 99%

Molecular testing for melanocytic tumors: a practical update

Andea

2021

Histopathology

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The work‐up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice.

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DNA copy number changes correlate with clinical behavior in melanocytic neoplasms: proposal of an algorithmic approach

Cited by 23 publications

References 28 publications

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis

Molecular testing for melanocytic tumors: a practical update

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