Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Somatic variant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1999

Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation.

The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma.

Carcinoma, Medullary↗
PubMed2026

Survey of diagnostic laboratories highlights need for improved standards in somatic genomic testing and reporting.

There is a growing international need to support somatic genomic testing, standardised variant curation and improved patient access to molecular profiling for somatic conditions, including cancer. We conducted a survey of scope, curation, reporting and sharing practices of diagnostic laboratories performing somatic testing in Australia and New Zealand. Laboratories with accreditation (n = 41) were invited in 2023 to complete a semi-structured, 25-question interview. Responses were received for 27 laboratories (66% response rate) offering solid tumour, haematological malignancy and non-cancer services. Only 36% of laboratories offered tests capturing the full breadth of variants, from single-nucleotide variants to gene fusions. Knowledge sharing was rare, with only one laboratory submitting variant classifications to a public knowledge base. Most laboratories (96%) conducted somatic testing in oncology. Of cancer laboratories, 35% offered testing considered capable of comprehensive genomic profiling (CGP). Almost half of cancer laboratories had already adopted the 2022 ClinGen/CGC/VICC oncogenicity guidelines, and 84% were using AMP/ASCO/CAP 2017 clinical significance guidelines. Only 47% of mixed discipline cancer laboratories reported biomarkers such as tumour mutational burden, with wide variation in reporting of matched therapy options. Our study has generated a unique overview of somatic laboratory practices in the region, and areas for global standardisation in somatic molecular testing and reporting. We also provide a model for practice and guideline uptake assessment, for application by other country-wide networks. This is particularly relevant in anticipation of CGP mainstreaming, with the increasing complexity of sequencing interpretation for laboratories and clinicians.

Humans↗
PubMed2002

Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors.

In an attempt to progress in the understanding of the relationship of mitochondrial DNA (mtDNA) alterations and thyroid tumorigenesis, we studied the mtDNA in 79 benign and malignant tumors (43 Hürthle and 36 non-Hürthle cell neoplasms) and respective normal parenchyma. The mtDNA common deletion (CD) was evaluated by semiquantitative polymerase chain reaction. Somatic point mutations and sequence variants of mtDNA were searched for in 66 tumors (59 patients) and adjacent parenchyma by direct sequencing of 70% of the mitochondrial genome (including all of the 13 OXPHOS system genes). We detected 57 somatic mutations, mostly transitions, in 34 tumors and 253 sequence variants in 59 patients. Follicular and papillary carcinomas carried a significantly higher prevalence of non-silent point mutations of complex I genes than adenomas. We also detected a significantly higher prevalence of complex I and complex IV sequence variants in the normal parenchyma adjacent to the malignant tumors. Every Hürthle cell tumor displayed a relatively high percentage (up to 16%) of mtDNA CD independently of the lesion's histotype. The percentage of deleted mtDNA molecules was significantly higher in tumors with D-loop mutations than in mtDNA stable tumors. Sequence variants of the ATPase 6 gene, one of the complex V genes thought to play a role in mtDNA maintenance and integrity in yeast, were significantly more prevalent in patients with Hürthle cell tumors than in patients with non-Hürthle cell neoplasms. We conclude that mtDNA variants and mtDNA somatic mutations of complex I and complex IV genes seem to be involved in thyroid tumorigenesis. Germline polymorphisms of the ATPase 6 gene are associated with the occurrence of mtDNA CD, the hallmark of Hürthle cell tumors.

Adenoma, Oxyphilic↗
PubMed2006

Mitochondrial DNA D-loop in pancreatic cancer: somatic mutations are epiphenomena while the germline 16519 T variant worsens metabolism and outcome.

We ascertained the frequency of mitochondrial DNA (mtDNA) D-loop region somatic mutations in pancreatic cancer (PC) and verified whether polymorphisms were linked to diagnosis, prognosis, and PC-associated diabetes mellitus (DM) in 99 PC cases, 42 chronic pancreatitis (CP) cases, 18 pancreatobiliary tract tumors, and 87 healthy control subjects (CSs). Tissue samples were obtained from 19 patients with PC and 5 with CP. The D-loop region was sequenced from all tissue samples and from blood DNA of the same patients and 12 CSs. D-loop somatic mutations were found in 3 PC tissue samples (16%). Four single nucleotide polymorphisms (SNPs; T152C, T16189C, T16519C, A73G), more frequently found in PC than in CS, were analyzed by denaturing high-performance liquid chromatography-restriction fragment length polymorphism using blood DNA as the starting template in all cases. The T allele of 16519 SNP correlated with DM. The survival of patients with PC correlated with tumor stage and grade and with DM at diagnosis. When survival analysis was performed considering only patients with locally advanced disease, the T allele of mtDNA 16519 SNP correlated with shorter life expectancy. mtDNA D-loop somatic mutations, rarely found in PC, cannot be considered causative events for this tumor type and probably are epiphenomena; the mtDNA D-loop 16519 variant, which worsens PC prognosis, seems to be a predisposing genetic factor for DM.

Adenocarcinoma↗
PubMed2025

Somatic and germinal mosaicism of a canonical splicing variant causing limb-girdle muscular dystrophy type 1B.

Limb-girdle muscular dystrophy type 1B is one of several muscular dystrophies caused by pathogenic variants in the LMNA gene. In this study, we investigated the clinical, pathological, and genetic findings of an LGMD1B family. Genetic sequencing identified the proband and her younger brother both carried the canonical splicing c.513 + 1G > A variant in the LMNA gene. The variant was absent in the proband's mother, and a certain percentage of the LMNA variant was identified in the venous blood, urine, and semen sample of the proband's father by pyrophosphate sequencing. Further cDNA analysis demonstrated that the canonical splicing c.513 + 1G > A variant in intron 2 induced retention of the first 45 bp of intron 2, resulting in an in-frame insertion of 15 amino acids. Our study directly confirmed the presence of somatic and germinal mosaicism in the LGMD1B family and the pathogenicity of the canonical splicing variant in the LMNA gene.

Humans↗
PubMed1952

The somatic antigen of a phage-resistant variant of Phase II Shigella sonnei.

1. A phage-resistant variant of Phase II Shigella sonnei has been isolated and the type-specific antigen from it has been obtained. 2. The antigen of the variant microorganism, II/3, 4, 7, differs from that of the parent Phase II bacillus in serological specificity and in chemical make-up. 3. Although the antigen of Phase II Sh. sonnei inhibits all T phages to which the bacillus is susceptible, that of the variant fails to inhibit T(3), T(4), and T(7).

Antigens↗