Vincent Michaud, Angèle Sequeira, Elina Mercier, Eulalie Lasseaux, Claudio Plaisant, Smail Hadj-Rabia, Sandra Whalen, Dominique Bonneau, Anne Dieux-Coeslier, Fanny Morice-Picard, Juliette Coursimault, Benoît Arveiler, Sophie Javerzat
{"title":"Unsuspected consequences of synonymous and missense variants in OCA2 can be detected in blood cell RNA samples of patients with albinism","authors":"Vincent Michaud, Angèle Sequeira, Elina Mercier, Eulalie Lasseaux, Claudio Plaisant, Smail Hadj-Rabia, Sandra Whalen, Dominique Bonneau, Anne Dieux-Coeslier, Fanny Morice-Picard, Juliette Coursimault, Benoît Arveiler, Sophie Javerzat","doi":"10.1111/pcmr.13123","DOIUrl":"10.1111/pcmr.13123","url":null,"abstract":"<p>Oculocutaneous albinism type 2 (OCA2) is the second most frequent form of albinism and represents about 30% of OCA worldwide. As with all types of OCA, patients present with hypopigmentation of hair and skin, as well as severe visual abnormalities. We focused on a subgroup of 29 patients for whom genetic diagnosis was pending because at least one of their identified variants in or around exon 10 of <i>OCA2</i> is of uncertain significance (VUS). By minigene assay, we investigated the effect of these VUS on exon 10 skipping and showed that not only intronic but also some synonymous variants can result in enhanced exon skipping. We further found that excessive skipping of exon 10 could be detected directly on blood samples of patients and of their one parent with the causal variant, avoiding invasive skin biopsies. Moreover, we show that variants, which result in lack of detectable <i>OCA2</i> mRNA can be identified from blood samples as well, as shown for the most common <i>OCA2</i> pathogenic missense variant c.1327G>A/p.(Val443Ile). In conclusion, blood cell RNA analysis allows testing the potential effect of any <i>OCA2</i> VUS on transcription products. This should help to elucidate yet unsolved OCA2 patients and improve genetic counseling.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 5","pages":"534-545"},"PeriodicalIF":3.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Courtney K. Wallingford, Ellie J. Maas, Antonia Howard, Emily DeBortoli, Deboshmita Bhanja, Katie Lee, Adam Mothershaw, Kasturee Jagirdar, Rod Willett, Brigid Betz-Stablein, Richard A. Sturm, H. Peter Soyer, Aideen M. McInerney-Leo
{"title":"MITF E318K: A rare homozygous case with multiple primary melanoma","authors":"Courtney K. Wallingford, Ellie J. Maas, Antonia Howard, Emily DeBortoli, Deboshmita Bhanja, Katie Lee, Adam Mothershaw, Kasturee Jagirdar, Rod Willett, Brigid Betz-Stablein, Richard A. Sturm, H. Peter Soyer, Aideen M. McInerney-Leo","doi":"10.1111/pcmr.13122","DOIUrl":"10.1111/pcmr.13122","url":null,"abstract":"<p><i>MITF</i> E318K moderates melanoma risk. Only five <i>MITF</i> E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous <i>MITF</i> E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (<i>n</i> = 162) with pigmentation varying from light to dark. Most naevi generally (<i>n</i> = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (<i>n</i> = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the <i>MITF</i> E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"68-73"},"PeriodicalIF":4.3,"publicationDate":"2023-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inna Smalley, Adrienne Boire, Priscilla Brastianos, Harriet M. Kluger, Eva Hernando-Monge, Peter A. Forsyth, Kamran A. Ahmed, Keiran S. M. Smalley, Sherise Ferguson, Michael A. Davies, Isabella C. Glitza Oliva
{"title":"Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care","authors":"Inna Smalley, Adrienne Boire, Priscilla Brastianos, Harriet M. Kluger, Eva Hernando-Monge, Peter A. Forsyth, Kamran A. Ahmed, Keiran S. M. Smalley, Sherise Ferguson, Michael A. Davies, Isabella C. Glitza Oliva","doi":"10.1111/pcmr.13116","DOIUrl":"10.1111/pcmr.13116","url":null,"abstract":"<p>Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"51-67"},"PeriodicalIF":4.3,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Zeng, Hung Long Ngo, Martina Proctor, Helen Rizos, Riccardo Dolcetti, Jazmina Gonzalez Cruz, James W. Wells, Brian Gabrielli
{"title":"Checkpoint kinase 1 inhibitor + low-dose hydroxyurea efficiently kills BRAF inhibitor- and immune checkpoint inhibitor-resistant melanomas","authors":"Zhen Zeng, Hung Long Ngo, Martina Proctor, Helen Rizos, Riccardo Dolcetti, Jazmina Gonzalez Cruz, James W. Wells, Brian Gabrielli","doi":"10.1111/pcmr.13120","DOIUrl":"10.1111/pcmr.13120","url":null,"abstract":"<p>Treatment of melanomas with targeted and immunotherapies has proven effective, but resistance to both treatments is a common outcome leaving a high proportion of patients without effective alternative treatment options. Replication stress is a common feature of melanomas, and this is effectively targeted using a combination of checkpoint kinase 1 (CHK1) inhibitor and low-dose hydroxyurea (LDHU). This combination also promotes inflammatory and anti-tumour immune responses in vivo. Melanoma cell lines resistant to BRAF inhibitor (BRAFi) or immune checkpoint inhibitors (ICI) retain their sensitivity to CHK1i + LDHU, with sensitivity similar to that of parental tumours. In vivo, BRAFi-resistant and BRAFi-sensitive parental tumours produce an identical immune response with treatment.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"45-50"},"PeriodicalIF":4.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activated Akt expression is associated with the recurrence of primary melanomas and further refines the prognostic and predictive values for relapse in acral melanomas","authors":"Kohei Nojima, Masahiro Hayashi, Atsushi Tanemura, Hind Al-Busani, Toru Saito, Tamio Suzuki, Masashi Ishikawa, Taisuke Mori, Shogo Wada, Naoya Yamazaki, Ichiro Katayama, Hiroki Mori, Hiroo Yokozeki, Naoko Okiyama, Yoshiyuki Sasaki, Takeshi Namiki","doi":"10.1111/pcmr.13119","DOIUrl":"10.1111/pcmr.13119","url":null,"abstract":"<p>A <i>PTEN</i> deficiency leads to the activation of phospho-Akt at serine 473 (<i>p</i>-Akt) and promotes the tumorigenesis of melanomas by coupling with <i>NUAK2</i> amplification. We tested the prognostic impact of <i>p</i>-Akt and/or NUAK2 expression on the relapse-free survival (RFS) and overall survival (OS) of melanoma patients. Primary tumors from patients with acral melanomas (112), Low-cumulative sun damage (CSD) melanomas (38), and High-CSD melanomas (18) were examined using immunohistochemistry and their prognostic significance was analyzed statistically. The expression of <i>p</i>-Akt was found in 32.1%, 68.4%, and 55.6% of acral, Low-CSD, and High-CSD melanomas, while NUAK2 expression was found in 46.4%, 76.3%, and 50.0%, respectively. Either <i>p</i>-Akt or NUAK2 expression was inversely correlated with the RFS of primary melanoma patients and acral melanoma patients (<i>p</i>-Akt: <i>p</i> < .0001, <i>p</i> < .0001; NUAK2; <i>p</i> = .0005, <i>p</i> < .0001, respectively). Strikingly, multivariate analyses revealed that <i>p</i>-Akt had a significant impact on RFS (Hazard ratio = 4.454; <i>p</i> < .0001), while NUAK2 did not. Further subset analyses revealed that <i>p</i>-Akt expression had an inferior RFS of patients with acral melanomas (Hazard ratio = 4.036; <i>p</i> = .0005). We conclude that the expression of <i>p</i>-Akt has a significant impact on RFS of patients with primary melanomas and can predict the relapse of patients with acral melanomas.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"36-44"},"PeriodicalIF":4.3,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sancy A. Leachman, Emile Latour, Brian Detweiler-Bedell, Jerusha B. Detweiler-Bedell, Adrienne Zell, Elizabeth Wenzel, Elizabeth Stoos, Jacob H. Nelson, Jack Wiedrick, Elizabeth G. Berry, Jane Lange, Ruth Etzioni, Jodi A. Lapidus
{"title":"Melanoma literacy among the general population of three western US states","authors":"Sancy A. Leachman, Emile Latour, Brian Detweiler-Bedell, Jerusha B. Detweiler-Bedell, Adrienne Zell, Elizabeth Wenzel, Elizabeth Stoos, Jacob H. Nelson, Jack Wiedrick, Elizabeth G. Berry, Jane Lange, Ruth Etzioni, Jodi A. Lapidus","doi":"10.1111/pcmr.13106","DOIUrl":"10.1111/pcmr.13106","url":null,"abstract":"<p>Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self-examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high-incidence US states, 15,000 surveys were sent to a population-representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self-reported SSE and its association with melanoma literacy, self-efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being “fairly” or “very” confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self-efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"481-500"},"PeriodicalIF":4.3,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modeling of pigmentation disorders associated with MITF mutation in Waardenburg syndrome revealed an impaired melanogenesis pathway in iPS-derived melanocytes","authors":"Jie Wen, Jian Song, Jiale Chen, Zhili Feng, Qiancheng Jing, Wei Gong, Xiaoming Kang, Lingyun Mei, Chufeng He, Lu Ma, Yong Feng","doi":"10.1111/pcmr.13118","DOIUrl":"10.1111/pcmr.13118","url":null,"abstract":"<p>Waardenburg Syndrome (WS) is a rare genetic disorder that leads to congenital hearing loss and pigmentation defects. Microphthalmia-associated transcription factor (<i>MITF</i>) is one of its significant pathogenic genes. Despite the comprehensive investigation in animal models, the pathogenic mechanism is still poorly described in humans due to difficulties accessing embryonic tissues. In this work, we used induced pluripotent stem cells derived from a WS patient carrying a heterozygous mutation in the <i>MITF</i> gene c.626A>T (p.His209Leu), and differentiated toward melanocyte lineage, which is the most affected cell type involved in WS. Compared with the wild-type cell line, the <i>MITF</i><sup>mut</sup> cell line showed a reduced expression of the characteristic melanocyte-related genes and a lesser proportion of mature, fully pigmented melanosomes. The transcriptome analysis also revealed widespread gene expression changes at the melanocyte stage in the <i>MITF</i><sup>mut</sup> cell line. The differentially expressed genes were enriched in melanogenesis and cell proliferation-related pathways. Interestingly, ion transport-related genes also showed a significant difference in <i>MITF</i><sup>mut</sup>-induced melanocytes, indicating that the <i>MITF</i> mutant may lead to the dysfunction of potassium channels and transporters produced by intermediate cells in the cochlea, further causing the associated phenotype of deafness. Altogether, our study provides valuable insights into how <i>MITF</i> mutation affects WS patients, which might result in defective melanocyte development and the related phenotype based on the patient-derived iPSC model.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"21-35"},"PeriodicalIF":4.3,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. S. W. Borgers, F. H. Burgers, A. Schina, O. J. Van Not, A. J. M. van den Eertwegh, C. U. Blank, M. J. B. Aarts, F. W. P. J. van den Berkmortel, J. W. B. de Groot, G. A. P. Hospers, E. Kapiteijn, D. Piersma, R. S. van Rijn, A. M. Stevense-den Boer, A. A. M. van der Veldt, G. Vreugdenhil, M. J. Boers-Sonderen, M. W. J. M. Wouters, K. P. M. Suijkerbuijk, J. V. van Thienen, J. B. A. G. Haanen
{"title":"Seasonal variation of anti-PD-1 outcome in melanoma—Results from a Dutch patient cohort","authors":"J. S. W. Borgers, F. H. Burgers, A. Schina, O. J. Van Not, A. J. M. van den Eertwegh, C. U. Blank, M. J. B. Aarts, F. W. P. J. van den Berkmortel, J. W. B. de Groot, G. A. P. Hospers, E. Kapiteijn, D. Piersma, R. S. van Rijn, A. M. Stevense-den Boer, A. A. M. van der Veldt, G. Vreugdenhil, M. J. Boers-Sonderen, M. W. J. M. Wouters, K. P. M. Suijkerbuijk, J. V. van Thienen, J. B. A. G. Haanen","doi":"10.1111/pcmr.13117","DOIUrl":"10.1111/pcmr.13117","url":null,"abstract":"<p>Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long-term) benefit from these treatments. There is evidence that the exposome, an accumulation of host-extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with <i>BRAF</i> wild-type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host-extrinsic factor influences the response to ICI-treatment.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"15-20"},"PeriodicalIF":4.3,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/pcmr.13117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10237502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophie S. Lim, Tasneem F. Mohammad, Indermeet Kohli, Iltefat Hamzavi, Michelle Rodrigues
{"title":"Optimisation of skin phototype classification","authors":"Sophie S. Lim, Tasneem F. Mohammad, Indermeet Kohli, Iltefat Hamzavi, Michelle Rodrigues","doi":"10.1111/pcmr.13110","DOIUrl":"10.1111/pcmr.13110","url":null,"abstract":"<p>Understanding individuals' skin pigmentation and photosensitivity is important in judging risk of skin cancer and response to certain treatment modalities. However, individuals with darkly pigmented skin are poorly represented in the widely used Fitzpatrick skin phototype (FST) system. Moreover, the FST system is prone to misuse, as it relies on subjective patient and clinician assessment of skin type, and does not clearly differentiate pigmentation from photosensitivity. By evaluating the key literature surrounding the FST system, its criticisms and proposed alternatives, this review serves to understand how skin phototype classification can be optimised.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"36 6","pages":"468-471"},"PeriodicalIF":4.3,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10310680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ifeoma U. Perkins, Serena Y. Tan, Timothy H. McCalmont, Pauline M. Chou, Thaddeus W. Mully, Pedram Gerami, Jason H. Pomerantz, Miguel Reyes-Múgica, Daniel M. Balkin, Lacey L. Kruse, Benjamin Huang, Jennifer L. Reichek, Noopur Gangopadhyay, Simon Chiosea, Jared R. Green, Sarah L. Chamlin, Ilona J. Frieden, Boris C. Bastian, Iwei Yeh
{"title":"Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK)","authors":"Ifeoma U. Perkins, Serena Y. Tan, Timothy H. McCalmont, Pauline M. Chou, Thaddeus W. Mully, Pedram Gerami, Jason H. Pomerantz, Miguel Reyes-Múgica, Daniel M. Balkin, Lacey L. Kruse, Benjamin Huang, Jennifer L. Reichek, Noopur Gangopadhyay, Simon Chiosea, Jared R. Green, Sarah L. Chamlin, Ilona J. Frieden, Boris C. Bastian, Iwei Yeh","doi":"10.1111/pcmr.13115","DOIUrl":"10.1111/pcmr.13115","url":null,"abstract":"<p>We describe the first cases of pediatric melanoma with <i>ALK</i> fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in <i>NRAS</i> and <i>BRAF</i> were absent in both cases. Instead, oncogenic <i>ZEB2</i>::<i>ALK</i> fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with <i>ALK</i> fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar <i>ALK</i> fusion kinases, identifying <i>ALK</i> fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":"37 1","pages":"6-14"},"PeriodicalIF":4.3,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9843171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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