Rates of ERBB2 alterations across melanoma subtypes and a complete response to trastuzumab emtansine in an ERBB2-amplified acral melanoma Journal Article


Authors: Gottesdiener, L. S.; O'Connor, S.; Busam, K. J.; Won, H.; Solit, D. B.; Hyman, D. M.; Shoushtari, A. N.
Article Title: Rates of ERBB2 alterations across melanoma subtypes and a complete response to trastuzumab emtansine in an ERBB2-amplified acral melanoma
Abstract: Purpose: Patients with BRAF V600 wild-type melanoma whose tumors progress on checkpoint inhibition currently have limited therapeutic options, and additional rational treatment targets are needed. ERBB2 alterations may be amenable to targeted inhibition, but the rate of ERBB2 alterations across melanoma subtypes is not well described. Patients and Methods: All patients with nonuveal melanoma (cutaneous, acral, mucosal, and unknown primary) whose tumors underwent multigene sequencing with MSK-IMPACT at Memorial Sloan Kettering Cancer Center (New York, NY) from 2014 to 2018 were reviewed for known or likely oncogenic somatic alterations in ERBB2 and the other known canonical driver genes BRAF, NRAS, KIT, NF1, GNAQ, and GNA11. Results: A patient with acral melanoma resistant to checkpoint inhibition was found to have ERBB2 amplification and achieved a durable complete response to trastuzumab emtansine. Tumor sequencing results from 732 melanoma cases were analyzed for ERBB2 and canonical driver gene alterations. ERBB2 amplifications were detected in acral (3%) and mucosal (3%) melanomas. ERBB2 mutations were found in cutaneous (1%), acral (2%), and mucosal (2%) subtypes and frequently cooccurred with NF1 alterations. Among the 140 patients whose tumors lacked canonical driver alterations, ERBB2 amplifications were detected in acral (7%) and mucosal (6%) melanomas. Conclusions: ERBB2 amplification is present in a minority of acral lentiginous and mucosal melanomas. Activating mutations in ERBB2 were identified in nonuveal melanoma subtypes and are frequently comutated with canonical drivers. HER2 could represent a therapeutically relevant target across melanoma subtypes. ©2018 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 24
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2018-12-01
Start Page: 5815
End Page: 5819
Language: English
DOI: 10.1158/1078-0432.Ccr-18-1397
PROVIDER: scopus
PUBMED: 30093446
DOI/URL:
Notes: Clin. Cancer Res. -- Export Date: 2 January 2019 -- Article -- CODEN: CCREF -- Source: Scopus
Altmetric Score
MSK Authors
  1. David Solit
    431 Solit
  2. David Hyman
    181 Hyman
  3. Klaus J Busam
    536 Busam
  4. Helen Hyeong-Eun Won
    79 Won