The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in the same human melanoma
Abstract
Activating BRAF or NRAS mutations have been found in 80% of human sporadic melanomas, but only one of these genetic alterations could be detected in each tumour. This suggests that BRAF and NRAS 'double mutants' may not provide advantage for tumour growth, or may even be selected against during tumorigenesis. However, by applying mutant-allele-specific-amplification-PCR method to short-term melanoma lines, one out of 14 tumours was found to harbour both BRAFV600E and the activating NRASQ61R mutations. On the other hand, analysis of 21 melanoma clones isolated by growth in soft agar from this tumour indicated that 16/21 clones harboured a BRAFV600E, but were wild-type for NRAS, whereas the remaining had the opposite genotype (NRASQ61R/wild-type BRAF). When compared to BRAFV600E clones, NRASQ61R clones displayed reduced growth in soft agar, but higher proliferative ability in vitro in liquid medium and even in vivo after grafting into SCID/SCID mice. These data suggest that NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level. Moreover, the presence of NRASQ61R or BRAFV600E is associated with distinct in vitro and in vivo growth properties of neoplastic cells.
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“Several KRAS alleles had reduced comutation with NRAS and BRAF, and increased comutation with APC and PIK3CA”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [42]
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Metadata
- Authors
- Sensi, M., Nicolini, G., Petti, C., Bersani, I., Lozupone, F., Molla, A., Vegetti, C., Nonaka, D., Mortarini, R., Parmiani, G., Fais, S., & Anichini, A.
- Affiliations
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Sensi, M
- Venue
- Oncogene
- Published
- 2006-02-06
- Volume
- 25
- Issue
- 24
- Pages
- 3357-3364
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2057818550
- Cited by
- 183
- References
- 33
- Citations by year
- 2026: 2 · 2024: 8 · 2023: 4 · 2022: 14 · 2021: 13 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 11 · 2015: 17 · 2014: 14 · 2013: 8 · 2012: 13
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- melanoma, NRAS Q61R mutation, BRAF V600E mutation, co-occurring mutations, mutually exclusive mutations, single-cell analysis, soft agar growth, tumorigenicity, SCID mouse xenograft
- MeSH terms
- Animals, Base Sequence, Female, Genotype, Humans, Melanoma, Molecular Sequence Data, Mutation, Neoplasm Transplantation, Genes, ras, Mice, SCID, Cell Line, Tumor, Proto-Oncogene Proteins B-raf, Mice
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