Whole-Exome Sequencing Reveals Somatic Mutations in HRAS and KRAS , which Cause Nevus Sebaceus

Levinsohn, Jonathan L.; Tian, Li C.; Boyden, Lynn M.; McNiff, Jennifer M.; Narayan, Deepak; Loring, Erin S.; Dai, Yun; Sugarman, Jeffrey; Overton, John D.; Mane, Shrikant; Lifton, Richard P.; Paller, Amy S.; Wagner, Annette; Antaya, Richard J.; Choate, Keith

doi:10.1038/jid.2012.379

Cited by 83 publications

(90 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together with the results presented here and by others in this issue (Levinsohn et al , 2012), the cumulative data demonstrate that keratinocytic epidermal nevi and sebaceous nevi are both associated with activating HRAS p.Gly13Arg and KRAS p.Gly12Asp mutations, supporting the belief held by some clinicians they represent a spectrum of the same entity (Sybert, 2010). We postulate that the phenotypic difference between these nevi may be related to the extent of the mutation, as well as body site-specific embryologic patterns and environment.…”

supporting

confidence: 88%

Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome

Sun

Saggini

Sarin

et al. 2013

Journal of Investigative Dermatology

View full text Add to dashboard Cite

supporting

confidence: 88%

Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome

Sun

Saggini

Sarin

et al. 2013

Journal of Investigative Dermatology

View full text Add to dashboard Cite

“…The highest degree of caution is, thus, recommended before initiating anti-BRAF V600À therapies in patients presenting with this type of benign lesion because of the major risk of transformation. RAS mutations also occur other premalignant congenital or acquired premalignant lesions like nevus sebaceus or colon polyps for respective examples (30,31). In rare genetic backgrounds like the Costello syndrome with constitutional activation of a RAS protein the risk of developing a secondary tumor is also substantial.…”

Section: Discussionmentioning

confidence: 99%

Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

et al. 2016

View full text Add to dashboard Cite

BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation.

show abstract

“…Indeed, one can build on the case starting from the recent discovery that NSJ is a mosaic RASopathy, characterized by postzygotic mosaic mutations in the HRAS and KRAS genes with resultant constitutive activation of the MAPK and PI3K-Akt signaling pathways. [29][30][31] It is possible that these mutations may predispose certain individuals to the development of secondary tumors in NSJ by additional genetic events and from there on to malignant transformation and progression through stepwise accumulation of distinct genomic alterations.…”

Section: Discussionmentioning

confidence: 99%

A Histological Snapshot of Hypothetical Multistep Progression From Nevus Sebaceus to Invasive Syringocystadenocarcinoma Papilliferum

Parekh

Guerrero²,

Knapp³

et al. 2016

The American Journal of Dermatopathology

View full text Add to dashboard Cite

Syringocystadenocarcinoma papilliferum (SCACP) is an extremely rare adnexal neoplasm, believed to arise in a preexisting nevus sebaceus of Jadassohn (NSJ) through a multistep progression process. This hypothetical process involves an NSJ giving rise to syringocystadenoma papilliferum, which then presumably undergoes malignant transformation in rare circumstances to give rise to SCACP in situ, which finally progresses to an invasive SCACP. Of the 30 SCACP cases reported so far, none have documented the process from a birthmark to the final invasive lesion, with histological evidence of each step, in a single tumor. Here, the authors report just such a case. A 74-year-old man presented with a recently enlarging birthmark on the scalp. Excisional biopsy showed an invasive SCACP, in the background of SCACP in situ, syringocystadenoma papilliferum, and NSJ. Furthermore, this tumor showed a concurrent pigmented trichoblastoma and histological evidence of lymphovascular invasion, events that have not been documented with SCACP. Interestingly, all these component lesions were present on a single histological section of this solitary tumor. Regional lymph node metastasis, a rare occurrence in SCACP, was also present in this remarkable case. The authors discuss the implications of these findings in light of the review of relevant literature.

show abstract

Whole-Exome Sequencing Reveals Somatic Mutations in HRAS and KRAS , which Cause Nevus Sebaceus

Cited by 83 publications

References 12 publications

Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome

Mosaic Activating RAS Mutations in Nevus Sebaceus and Nevus Sebaceus Syndrome

Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization

A Histological Snapshot of Hypothetical Multistep Progression From Nevus Sebaceus to Invasive Syringocystadenocarcinoma Papilliferum

Contact Info

Product

Resources

About