The association of tumor characteristics, including genetic alterations in common cancer genes such as BRAF, EGFR, HER2, KRAS, NRAS, PIK3CA, and TP53 with local tumor control, was assessed.All statistical tests were two-sided.
Cell lines originating from HCL patients lack BRAF mutations but retain the typical piliferous morphology and the distinctive HCL immunophenotype, thus, constituting suitable tools for identifying alternative tumor genes and leukemic mechanisms in this malignancy.
In this review we have assessed the potential utility of a molecular test for somatically acquired mutations in B-RAF using thyroid malignancy as a model system according to 3 fundamental questions: would a test enhance our ability to distinguish benign from malignant, would a test unveil a risk factor not otherwise known, and would detecting a mutation enable a therapeutic option specific to those patients who carry the mutation?
With the advent of successful therapy targeting mutant BRAF, melanoma is leading the field of cancer research in the molecular approach to therapy of advanced disease.
We calculated and compared the diagnostic performances of cytology and cytology with BRAF(V600E) mutation analysis to detect malignancy among thyroid nodules according to ultrasound features and size.
This is true for targeted therapies using tyrosine kinase inhibitors for EGFR or BRAF mutant cancers, but is also an increasingly recognized problem for immunotherapies.
BRAF-activating mutations have been reported in several types of cancer, including melanoma ( approximately 70% of cases), thyroid (30-70%), ovarian (15-30%), and colorectal cancer (5-20%).
Whereas most BRAF mutations in human cancers involved V599 of BRAF, all of the four BRAF mutations in the NHLs involved other amino acids (one G468A, two G468R and one D593G).
BRAFV600E-positive recurrent patients were found (131)I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAFV600E were both (131)I-negative and (18)F-FDG positive.
Consistently, inhibition of SHP2 (also known as PTPN11), which links receptor tyrosine kinase signaling to the RAS-RAF-MEK-ERK pathway<sup>11,12</sup>, was shown to be ineffective in KRAS-mutant or BRAF-mutant cancer cell lines<sup>13</sup>.
In this review, we consider the mechanisms and clinical impacts of B-Raf mutations in cancer and discuss the implications for the patient in melanoma, thyroid cancer and colorectal cancer, where B-Raf mutations are particularly common.
The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all-positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all-negative group).
TP53 and U2AF1 mutations have been implicated in other myelomonocytic malignancies and we hypothesized that mutations in these genes may cosegregate in LCH patients according to BRAF mutation status.