Biomedical subjects

M Wiench

Publications and source records attributed to M Wiench.

9 recordsLinked to original sources

PubMed2001

Estimation of risk of inherited medullary thyroid carcinoma in apparent sporadic patients.

PURPOSE: The study was undertaken to evaluate the frequency of inherited medullary thyroid carcinoma (MTC) among patients with apparent sporadic disease. A stepwise algorithm was used depending on clinical indices and the age of patient at MTC diagnosis. PATIENTS AND METHODS: One hundred sixteen patients with MTC verified by postoperative pathologic examination were subjected to genetic analysis of RET exons 10, 11, 13, 14, and 16 by means of polymerase chain reaction, restriction endonuclease digestion, and DNA sequencing. RESULTS: Among 116 apparent sporadic MTC patients, we identified eleven (9.5%) RET germline mutation carriers. Seven of these (6.0%) were found by routine analysis (exons 10 and 11). The frequency of inherited disease among patients younger than 45 years at diagnosis was 10.2% by analysis of typical mutations in exons 10 and 11. Extended genetic analysis (sequencing of exons 11, 13, 14, and 16) yielded 6.1% additional diagnoses, giving a risk of 16.3% in this age group. One previously unreported mutation in exon 11 affected codon 649 (TCG>TTG, Ser>Leu). In the true sporadic MTC patients younger than 30 years at diagnosis, frequencies of 36% and 4.5% in polymorphic variants L769L and S836S, respectively, were observed. The frequency for L769L was higher than in older patients (P <.05). CONCLUSION: The frequency of inherited disease among apparent sporadic medullary thyroid carcinoma patients is close to 10% in the Polish population of MTC patients. The extended analysis of all known RET proto-oncogene mutation sites is obligatory in patients younger than 45 years at diagnosis, but we also see the need to analyze the impact of rarer mutations in older patients.

Adult↗

PubMed2001

Molecular changes in thyroid neoplasia.

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

Carcinoma, Papillary↗

PubMed2001

The genetic background of medullary thyroid carcinoma in young patients.

The study was undertaken to evaluate the frequency of RET polymorphisms at codons 769 and 836 in young medullary thyroid carcinoma (MTC) patients in whom the presence of a known germline mutation has been excluded. 40 patients aged 10-29 were subjected to genetic analysis of RET exons 10, 11, 13, 14 and 16 and compared to 140 older patients. The hereditary component occurred to be very high in young MTC patients: 57% carry the germline mutation, other 28% exhibit at least one rare polymorphic variant of RET. The observed allelic frequencies were 38% for polymorphic variant L769CTG and 6% for variant S836AGT. The results were significantly higher than those obtained in the group of older patients: 20% and 1% for L769CTG and S836AGT, respectively. Our results speak in favour that the polymorphism in RET codon 769 and 836 may also be a factor predisposing to the development of MTC in young age.

Adult↗

PubMed2001

[Thyroglobulin RT-PCR method for detection of lymph node metastases during the course of differentiated thyroid cancers].

UNLABELLED: In patients with a suspicion of recurrence of differentiated thyroid cancer with metastases to lymph nodes, detection of thyroglobulin (Tg) mRNA in fine needle biopsy material may support the interpretation of classic cytological examination in cases where it fails to detect lymph node involvement early enough. AIM: Prospective study of thyroglobulin mRNA detection in neck lymph nodes in patients with suspected differentiated thyroid cancer (DTC) metastases. MATERIAL: 70 nodes from 60 patients with suspected DTC recurrence were investigated. Patients with suspicion of lymph node metastases of other types of cancer were included as a control group. Thyroglobulin RT-PCR was conducted in residual material left after preparation of cytological smears from fine needle biopsy specimens. Primers spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and cDNA amplification were carried out using GADPH starters. RESULTS: Classical cytology confirmed nodal involvement in 22 of DTC patients, RT-PCR Tg was positive in 20 of them (91%). Among 48 patients with a suspicion of DTC recurrence and negative cytology, Tg mRNA was found twice. One positive RT-PCR result was confirmed by repeated cytology conducted 4-6 months later and followed by surgery. No positive result of RT-PCR was obtained with other head and neck malignancies. The overall specificity was estimated with 98%. CONCLUSIONS: RT-PCR Tg shows sufficient specificity to be applied in further studies estimating its usefulness in fine needle biopsy for early detection of lymph node metastases in differentiated thyroid cancer.

Biopsy, Needle↗

PubMed2001

[Consequences of clinical genetic analysis of RET proto-oncogene].

Preliminary results of treatment of inherited medullary thyroid carcinoma, diagnosed primarily with genetic analysis of mutation of protooncogene RET are presented. Among 16 carriers of mutation identical with mutation diagnosed earlier in proband, there were 4 patients with clinically obvious medullary thyroid carcinoma and 12 asymptomatic carriers. In all patients, in whom calcitonin level was increased preoperatively, its normalization was obtained. The paper summarizes these aspects of cooperation between geneticians and physicians in which diagnostic results influence clinical decisions (indication and time of thyroid and lymph nodes surgery and it's spectrum, range of diagnostic procedures towards pheochromocytoma and parathyroid hyperplasia in relation to the found mutation).

Adolescent↗

PubMed2001

[Proto-oncogene RET somatic mutations in medullary thyroid carcinoma].

UNLABELLED: Somatic mutations of the RET protooncogene are present in 23-68% cases of sporadic medullary thyroid carcinoma (MTC). The aim of the study was to introduce the RET somatic mutations analysis in tumor tissue as well as to evaluate their types and frequencies in postoperative specimens of MTC patients treated in the Center of Oncology in Gliwice. MATERIAL: 14 tumor tissues obtained from sporadic MTC patients and two control groups--six and four specimens from patients with MEN 2A and MEN 2B syndrome respectively. METHODS: Tumor tissue DNA isolation followed by PCR amplification of RET exons 10, 11, 13, 14, 16 and automated, fluorescent sequencing of PCR products. We identified somatic mutation ATG > ACG in codon 918, exon 16 in 7 of 14 (50%) of analyzed sporadic MTC cases. We also found one deletion/insertion mutation in RET exon 11 that encompasses cysteine codon 634 and has not been published so far. The types and frequencies of found RET gene mutations were similar to previously reported. The analysis of RET somatic mutations supports the differentiation between the sporadic and inherited MTC. The presence of somatic mutation and its simultaneous absence in the germline proves sporadic type of cancer.

Carcinoma, Medullary↗

PubMed2001

[Results of treating medullary thyroid carcinoma: the differences between sporadic and inherited forms].

Medullary thyroid carcinoma (MTC) can be divided into two subgroups: sporadic or inherited. Hereditary form of MTC is often believed to be form with better prognosis than sporadic one. In this study the differences in MTC prognosis in Polish population of patients was analyzed. The group of 169 patients with MTC was examined. Hereditary cancer was stated in 48 (28%) patients. The median age of disease onset was 41 years (from 7 to 71 years). Genetic examination of RET protooncogene was performed in all patients. The calcitonin and CEA serum level analysis and radiological and radioisotopic examinations were used for monitoring of the disease course. Nineteen cases of MEN 2A syndrome, 11 cases of MEN 2B one and 18 cases of non classified familial MTC were recognized among patients with inherited MTC. Significantly lower age of disease onset in inherited MTC than in sporadic one was observed (27 years vs. 43.7 years, p < 0.001). Local or nodal recurrence was observed in 22 (13%) patients, distant metastases were stated in 21 (12%) patients. Basal or stimulated serum calcitonin level was increased in 85 (50%) patients. No significant differences between sporadic and inherited disease were observed. Eight patients died during observation, including 3 patients with sporadic MTC and 5 patients with inherited MTC. The updated 10-year survival rate was 97% in patients with sporadic MTC; in hereditary MTC it was about 20% worse. The complications related to the presence of adrenal tumors were the main reason for death in MEN2 and no significant differences in the course of MTC itself were observed.

Adolescent↗

PubMed2001

[Rearrangement of the RET gene in papillary thyroid carcinoma].

The RET/PTC oncogenes, activated forms of the RET protooncogene, almost exclusively found in papillary thyroid carcinoma (PTC). What is more, the targeted expression of RET/PTC in mice leads to the development of thyroid tumors very similar to human PTCs. In all RET/PTC types the RET tyrosine kinase domain is fused to the N-terminus of ubiquitously expressed genes that is capable of ligand-independent dimerization. The majority of RET/PTC identified consists of two types which results from the inversion of chromosome 10: RET/PTC1 and RET/PTC3. The prevalence of RET/PTC in papillary thyroid carcinomas of thyroid varies widely from a few to about 80% with the highest frequency in tumors arising in children after ionizing radiation. In Polish population the frequency of RET rearrangements in papillary cancers is 27%, although, it was reported to be twice higher in young patients (50% in patients younger than 21 at operation). Correlation with clinical outcome as well as prognostic value of RET/PTC is controversial. Some authors suggest that it predicts metastases, others found rearranged RET in more favourable, slow growing tumors. RET/PTC3 seems to be associated with solid/follicular variant PTC and short latency period (it is found more frequently in children) whereas RET/PTC1--with classic PTC variant and long latency.

Animals↗

PubMed2001

Sequencing of caprine alpha-S1 casein cDNAs confirms the accuracy of the RT-PCR approach for detecting of the variants of the gene.

Polymorphism of the casein gene in goats determines milk processing quality and cheese flavour. The main 7 alleles belong to 4 groups: strong alleles A, B, C (which code for 3.6 g/l), medium allele E (1.6 g/1), weak alleles F and D (0.6 g/1) and zero allele, connected with lack of alphaS1 casein in milk. Milk cells (mononuclear milk cells plus epithelium cells) and peripheral blood mononuclear cells were mRNA sources for reverse transcription. Three specific primers were used for polymerase chain reaction, which enabled to differentiate between alleles from four expression groups. The length of PCR products varied since allele F has a 111- nucleotide (nt) deletion of exons 9-11, allele D has a deletion of 36 nt (exon 9), and the medium allele E is associated with a 457 nt insertion in the 19th non-coding exon. Sequencing of amplified fragments, performed on PCR products isolated from milk, confirmed the correctness of the RT-PCR - based alphaS1 casein genotyping method.

Journal Article↗