5 research outputs found
Telomere erosion in NF1 tumorigenesis
Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that
affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant
fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant
cause of morbidity and mortality in NF1 and currently there is no treatment or definite
prognostic biomarkers for these tumors. Telomere shortening has been documented
in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it
is considered that the ensuing genomic instability may facilitate clonal evolution and
the progression to malignancy. To evaluate the potential role of telomere dysfunction
in NF1-associated tumors, we undertook a comparative analysis of telomere length
in samples derived from 10 cutaneous and 10 diffused plexiform neurofibromas, and
19 MPNSTs. Telomere length was determined using high-resolution Single Telomere
Length Analysis (STELA). The mean Xp/Yp telomere length detected in MPNSTs, at
3.282 kb, was significantly shorter than that observed in both plexiform neurofibromas
(5.793 kb; [p = 0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The
telomere length distributions of MPNSTs were within the length-ranges in which
telomere fusion is detected and that confer a poor prognosis in other tumor types.
These data indicate that telomere length may play a role in driving genomic instability
and clonal progression in NF1-associated MPNSTs
Codon-precise, synthetic, antibody fragment libraries built using automated hexamer codon additions and validated through next generation sequencing
We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibraâ„¢: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR) in antibody fragment libraries and next generation sequencing (NGS) analysis of their quality and diversity
An emerging role for microRNAs in NF1 tumorigenesis
Abstract MicroRNAs (miRNAs) are a class of non-coding RNA, which have recently been shown to have a wide variety of regulatory functions in relation to gene expression. Since their identification nearly 20 years ago, miRNAs have been found to play an important role in cancer, including in neurofibromatosis type 1 (NF1)-associated tumours. NF1 is the most commonly inherited tumour predisposition syndrome and can lead to malignancy via the development of malignant peripheral nerve sheath tumours (MPNSTs). Although the mechanisms by which benign neurofibromas develop into MPNSTs still remain to be elucidated, it is becoming increasingly clear that miRNAs play a key role in this process and have the potential to be used as both diagnostic and prognostic markers of tumorigenesis.</p
An emerging role for microRNAs in NF1 tumorigenesis
MicroRNAs (miRNAs) are a class of non-coding RNA, which have recently been shown to have a wide variety of regulatory functions in relation to gene expression. Since their identification nearly 20 years ago, miRNAs have been found to play an important role in cancer, including in neurofibromatosis type 1 (NF1)-associated tumours. NF1 is the most commonly inherited tumour predisposition syndrome and can lead to malignancy via the development of malignant peripheral nerve sheath tumours (MPNSTs). Although the mechanisms by which benign neurofibromas develop into MPNSTs still remain to be elucidated, it is becoming increasingly clear that miRNAs play a key role in this process and have the potential to be used as both diagnostic and prognostic markers of tumorigenesis