Clinical outcome and pathologic features associated with NRAS mutation in cutaneous melanoma.

Devitt, Bianca; Liu, W.; Salemi, Rossella; Wolfe, Rory; Jw, Kelly; Dobrovic, A.; McArthur, Grant A.

doi:10.1200/jco.2010.28.15_suppl.8500

Cited by 3 publications

(5 citation statements)

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“…NRAS mutations have been mainly described in melanomas and leukemias and their prognostic significance has been unclear, with some data suggesting an association between mutant NRAS and a worse prognosis in melanoma. [40] , [41] , [42] In our study, there was a high prevalence of NRAS mutations in melanoma (44%), and uterine cancer (15%). The prevalence of NRAS mutations was higher than reported in other studies or in the COSMIC database (14–20%).…”

Section: Discussionsupporting

confidence: 48%

“…In colorectal cancer they are associated with a dismal prognosis, however, unlike KRAS mutations, BRAF mutations might not be predictive of lack of cetuximab benefit [46]. In melanoma, the prognostic significance of BRAF mutations is less obvious, although patients with BRAF mutant melanoma seem to respond very well to BRAF inhibitors [4], [42], [47]. In papillary thyroid cancer, BRAF mutations were found to upregulate microenviromental genes, which potentially increases tumor aggressiveness [48].…”

Section: Discussionmentioning

confidence: 99%

“… [46] In melanoma, the prognostic significance of BRAF mutations is less obvious, although patients with BRAF mutant melanoma seem to respond very well to BRAF inhibitors. [4] , [42] , [47] In papillary thyroid cancer, BRAF mutations were found to upregulate microenviromental genes, which potentially increases tumor aggressiveness. [48] In agreement with previously published data, our study showed a high prevalence of BRAF mutations in melanoma (44%) and, to much lesser extent, in thyroid, colorectal, and ovarian cancer (8%, 6%, and 5%, respectively).…”

Section: Discussionmentioning

confidence: 99%

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PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers

et al. 2011

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BackgroundOncogenic mutations of PIK3CA, RAS (KRAS, NRAS), and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis.MethodsTumor tissues from 504 patients with diverse cancers referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center starting in October 2008 were analyzed for PIK3CA, RAS (KRAS, NRAS), and BRAF mutations using polymerase chain reaction-based DNA sequencing.Results PIK3CA mutations were found in 54 (11%) of 504 patients tested; KRAS in 69 (19%) of 367; NRAS in 19 (8%) of 225; and BRAF in 31 (9%) of 361 patients. PIK3CA mutations were most frequent in squamous cervical (5/14, 36%), uterine (7/28, 25%), breast (6/29, 21%), and colorectal cancers (18/105, 17%); KRAS in pancreatic (5/9, 56%), colorectal (49/97, 51%), and uterine cancers (3/20, 15%); NRAS in melanoma (12/40, 30%), and uterine cancer (2/11, 18%); BRAF in melanoma (23/52, 44%), and colorectal cancer (5/88, 6%). Regardless of histology, KRAS mutations were found in 38% of patients with PIK3CA mutations compared to 16% of patients with wild-type (wt)PIK3CA (p = 0.001). In total, RAS (KRAS, NRAS) or BRAF mutations were found in 47% of patients with PIK3CA mutations vs. 24% of patients wtPIK3CA (p = 0.001). PIK3CA mutations were found in 28% of patients with KRAS mutations compared to 10% with wtKRAS (p = 0.001) and in 20% of patients with RAS (KRAS, NRAS) or BRAF mutations compared to 8% with wtRAS (KRAS, NRAS) or wtBRAF (p = 0.001).Conclusions PIK3CA, RAS (KRAS, NRAS), and BRAF mutations are frequent in diverse tumors. In a wide variety of tumors, PIK3CA mutations coexist with RAS (KRAS, NRAS) and BRAF mutations.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers

et al. 2011

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“…Conversely, in a large study of primary, as opposed to metastatic, melanoma, the presence of mitoses was associated with wild-type BRAF 4 and mutant NRAS. 27 Nevertheless, these findings support the concept that mutant BRAF melanoma is biologically heterogeneous or at least acts in concert with other genetic alterations to produce a particular phenotype. We also observed an association of wild-type BRAF with a history of multiple cutaneous primary melanomas.…”

Section: Discussionmentioning

confidence: 87%

Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma

Long

Menzies

Nagrial

et al. 2011

JCO

939

717

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“…Recently, it has been reported that NRAS-mutant primarymelanomasappeartohaveaworseprognosisthanwildtype or BRAF-mutant tumors, although time to death from relapsedateappearstobesimilar. 3 Responsetochemotherapy was not analyzed. Our observation suggests that a subset of NRAS-mutant melanoma may respond better to chemotherapy with the carboxamide alkylating agents, which have been standard melanoma therapy for the last 3 decades.…”

Section: Commentmentioning

confidence: 99%

NRAS-Mutant Melanoma: Response to Chemotherapy

Soon¹,

Algazi²,

Edward³

et al. 2011

Arch Dermatol

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Clinical outcome and pathologic features associated with NRAS mutation in cutaneous melanoma.

Cited by 3 publications

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PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers

PIK3CA Mutations Frequently Coexist with RAS and BRAF Mutations in Patients with Advanced Cancers

Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma

NRAS-Mutant Melanoma: Response to Chemotherapy

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