Concordance of somatic mutation profiles (BRAF, NRAS, and TERT) and tumoral PD-L1 in matched primary cutaneous and metastatic melanoma samples

Yang, Shi; Leone, Dominick; Biswas, Asok; Deng, April; Jukic, D.M.; Singh, Vikram; Sundram, Uma; Mahalingam, Meera

doi:10.1016/j.humpath.2018.08.002

Cited by 13 publications

(14 citation statements)

References 34 publications

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“…Several previous studies have described the heterogeneity of genetic alterations between primary and corresponding metastatic lesions in melanoma (19,(29)(30)(31). In our cohort, the concordance rates of BRAF, C-KIT, and NRAS mutations between paired primary and metastatic lesions were 94.0%, 97.7%, and 94.9%, respectively.…”

Section: Discussionsupporting

confidence: 50%

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Ren¹,

Zhang²,

Kong³

et al. 2022

Ann Transl Med

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Background: Discrepancies in genetic alterations found in melanoma are conspicuous between different ethnic groups. With the approval of BRAF-and MEK-targeted inhibitors in China, it is necessary to further elucidate the landscape of gene mutation in Chinese melanoma patients. Methods:The frequency and distribution of BRAF, C-KIT, and NRAS mutations in 691 melanoma patients was determined, and the statistical significance of correlations between different gene mutations and clinicopathological features was analyzed.Results: Among a total of 691 patients, BRAF mutation was found in 166 patients (24.0%), and V600E was the prominent genetic alteration (145/166, 87.3%). Statistical analyses showed that younger patients (<60) had a higher BRAF mutation rate than older patients (≥60, P=0.000), and the frequency of BRAF mutation was more likely to be lower in patients with the following: melanoma located in an extremity (P=0.000), acral-lentiginous melanoma subtype (P=0.000), thinner melanoma thickness (P=0.047), and no ulceration (P=0.030). The frequency of NRAS mutation was 12.6% (38/302), and primarily involved codon 61 in exon 3 and codon 12 in exon 2. Mutation of C-KIT was detected in 65 patients (9.4%), and the most common site of mutations was L576 in exon 11 (29/65, 44.6%). Patients with NRAS or C-KIT mutation had higher Clark level (P=0.035 and 0.047, respectively) and were more likely to have melanoma located in an extremity (P=0.003 and 0.009, respectively) than those without such mutation. The concordance of gene mutations between paired primary and metastatic lesions was 89.6% (60/67), and visceral metastases showed the highest distribution of gene mutations versus primary melanomas (100.0%) compared with lymph nodes (90.9%) and cutaneous metastases (83.3%). Conclusions:In this large cohort of Chinese melanoma patients, the frequencies of BRAF and NRAS mutations were lower than those observed in Caucasian cohorts, but the clinicopathological features of BRAF, C-KIT, and NRAS mutation were consistent. Paired primary and metastatic lesions showed high concordance of gene mutations.

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Section: Discussionsupporting

confidence: 50%

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Ren¹,

Zhang²,

Kong³

et al. 2022

Ann Transl Med

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“…Second, there are significant variations in PD‐L1 expression within the same tumour and between samples from different tumour sites in the same patient . Given the intratumour heterogeneity and in order to analyse the largest tumour area, we evaluated the expression of PD‐L1 on whole tissue sections, which can better reflect the distribution and type of cells expressing PD‐L1 and also allows assessing the relationship between PD‐L1 expression on tumour cells and on immune cells.…”

Section: Discussionmentioning

confidence: 99%

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Bence

Hofman

Chamorey

et al. 2019

Acad Dermatol Venereol

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Background Recent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD-L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas.Objectives We investigated whether the presence and the features of pretreatment CD8 + tumour-infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma.Methods In this retrospective study, we evaluated the association of PD-L1 expression ≥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non-ICIs).Results PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (j = 0.283). No significant association was noted between PD-L1 expression and CD8 + TIL profile analysed as single markers and OS or response to immunotherapy.Instead, their combined analysis in primary melanoma samples showed that the PD-L1À/CD8 + status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non-ICIs (P = 0.009). Conversely, the PD-L1+/CD8 + status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non-ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8 + TIL+/PD-L1À (P = 0.02). ConclusionsThe pretreatment combination of PD-L1 expression with the level of CD8 + TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens. JEADV Funding sourceThis work did not receive any financial specific support.

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“…The gene encodes the catalytic subunit of telomerase, a ribonucleic complex that maintains telomere length, and plays an important role in tumour occurrence and cell immortality, and two mutation hotspots have been reported in the gene’s initiators: C228T and C250T [ 35 , 36 ]. BRAF mutations and TERT promoter mutations have synergies in the diagnosis of thyroid cancer [ 37 – 42 ], and we have also found synergies between BRAF mutations and TERT promoter mutations in patients with melanomas [ 43 – 45 ], epithelial glioblastomas [ 46 ] and gliomas [ 47 ]. BRAF V600E and TERT promoters at the same time mutation led to poor prognosis of thyroid papilloma cancer, which provides a certain reference value for diagnosis and treatment [ 48 ], but it still has some limitations.…”

Section: Tumour Suppressor Gene Methylation and Braf Gene Mutation In Tcmentioning

confidence: 93%

Epigenetic modification and BRAF gene mutation in thyroid carcinoma

et al. 2021

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Thyroid cancer remains the most prevailing endocrine malignancy, and a progressively increasing incidence rate has been observed in recent years, with 95% of thyroid cancer represented by differentiated thyroid carcinomas. The genetics and epigenetics of thyroid cancer are gradually increasing, and gene mutations and methylation changes play an important roles in its occurrence and development. Although the role of RAS and BRAF mutations in thyroid cancer have been partially clarified,but the pathogenesis and molecular mechanisms of thyroid cancer remain to be elucidated. Epigenetic modification refer to genetic modification that does not change the DNA sequence of a gene but causes heritable phenotypic changes in its expression. Epigenetic modification mainly includes four aspects: DNA methylation, chromatin remodelling, noncoding RNA regulation, and histone modification. This article reviews the importance of thyroid cancer epigenetic modification and BRAF gene mutation in the treatment of thyroid cancer.

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Concordance of somatic mutation profiles (BRAF, NRAS, and TERT) and tumoral PD-L1 in matched primary cutaneous and metastatic melanoma samples

Cited by 13 publications

References 34 publications

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

BRAF, C-KIT, and NRAS mutations correlated with different clinicopathological features: an analysis of 691 melanoma patients from a single center

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Epigenetic modification and BRAF gene mutation in thyroid carcinoma

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