Search results for "MUTATION"
showing 10 items of 2830 documents
4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily).
2007
Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…
Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana
2019
[Background]: Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen.
Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting…
2020
Abstract Background PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established. Results We have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprintin…
Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects
2014
et al.
Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone
2012
Abstract Background Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce. Methods We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed a…
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia
2013
Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status i…
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.
2014
The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared …
Somatic mutation profiles as molecular classifiers of ulcerative colitis-associated colorectal cancer.
2021
Ulcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question by determining the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). The findings were compared to Lynch syndrome (LS), a different form of cancer predisposition that shares the importance of immunological factors in tumorigenesis. CA-CRCs (n=27) were investigated for microsatellite instability, CpG island methylator phenotype, and somatic mutations of 999 cancer-relevant genes ("Pan-cancer" panel). A subpanel of "Pan-cancer" design (578 genes) was used for LS colorectal tumors (n=28). Mutational loads and signatures stratifie…
Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer
2015
BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway has been implicated in the molecular pathogenesis of human cancers, including metastatic colorectal cancer (mCRC). This provides a rationale for the development of MAPK-targeted agents such as pimasertib. METHODS: Patients with KRAS mutant mCRC were treated in the second-line setting with FOLFIRI (5-fluorouracil/folinic acid/irinotecan) plus pimasertib. The primary objective of the safety run-in phase was to determine the maximum-tolerated dose (MTD) and the recommended phase II dose of pimasertib combined with FOLFIRI. RESULTS: Sixteen patients were enrolled in the trial. Ten and six patients were treated daily with 45 and 60 …
Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene
2016
Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation-negative MBC cases.Germ-line DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 …