Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

<p>Abstract</p> <p>Background</p> <p>Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the <it>CDK4 </it>gene reported to date. Beside those high penetrance genes, certain allelic variants of the <it>MC1R </it>gene modify the risk of developing the disease.</p> <p>The aims of our study were: to determine the prevalence of germline <it>CDKN2A </it>mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible <it>CDK4 </it>mutations, and to determine the frequency of variations in the <it>MC1R </it>gene.</p> <p>Methods</p> <p>From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing.</p> <p>Results</p> <p>Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the <it>CDK4 </it>gene were found.</p> <p>Most frequently found variants of the <it>MC1R </it>gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant.</p> <p>Conclusion</p> <p>The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or <it>CDK4 </it>mutations.</p

31. Analiza mutacji w genie NBS1 u chorych na czerniaka

Gen NBS1 zlokalizowany na chromosomie 8 (8p21) koduje białko – nibrynę, która wchodzi w skład systemu naprawczego dwuniciowych pęknięć DNA, kompleksu zaangażowanego w rekombinacje chromosomów mejotycznych oraz kompleksu utrzymującego homeostazę telomerów. Homozygotyczna mutacja 657del5 tego genu jest przyczyną zespołu Nijmegen, recesywnie dziedziczonej choroby dysmorficznej. U heterozygotycznych nosicieli mutacji w genie NBS1 657del5, R215W) obserwowana jest zwiększona zachorowalność na nowotwory, w tym również na czerniaka. Celem pracy było ustalenie częstości występowania mutacji w genie NBS1 u chorych na czerniaka. Przebadano 391 chorych na czerniaka, w tym bez obciążonego wywiadu rodzinnego 341. W przypadku 50 chorych u 8 występowały 1 lub 2 czerniaki w rodzinie, u 10 nowotwory płuc, u 8 nowotwory piersi, u 8 nowotwory żołądka, u 6 rak szyjki macicy, u 5 rak prostaty, pozostali wykazywali w wywiadzie występowanie nowotworów nerek, krtani, mózgu, trzustki, białaczki. DNA do badań genetycznych izolowano z limfocytów krwi obwodowej osób chorych stosując zestaw Wizard firmy Promega. Do wyszukiwania mutacji zastosowano technikę PCR-SSCP, posługując się zestawem 19 par starterów analizowano cały gen. Pasma wykazujące zmienioną migrację w żelu wycinano i poddawano sekwencjonowaniu. Dodatkowo do poszukiwania najczęściej występującej w tej genie mutacji – 657del5 wykorzystano multipleksowy PCR. W trakcie prowadzonych analiz zidentyfikowano tylko 4 mutacje weksonie 6 – R215W. Mutacja ta została wykryta u osób niemających historii rodzinnej zachorowań na nowotwory. Jej częstość i patogenność nie została dotąd ostatecznie ustalona, w przeciwieństwie do najczęściej opisywanej mutacji w tym genie 657del5, której nosicielstwo szacuje się na 1/100 – 1-300 w zależności od regionu

Impact of COVID-19 on the performance of a radiation oncology department at a major comprehensive cancer centre in Poland during the first ten weeks of the epidemic

The outbreak of SARS-CoV-2 coronavirus rapidly altered radiotherapy service delivery around the world.AimThe main objective of this study was to assess the impact of precautionary measures implemented in response to the COVID-19 pandemic on the performance of a radiation oncology departments and on mitigation the risk of COVID-19 contagion between and among patients and staff.MethodsThe study period was from March 15 until May 22, 2020. We evaluated total number of patients irradiated and those who initiated treatments, taking into account tumours localisations. We assessed the relationship of potential risk of contagion with patients’ domiciles locations in regions with high number of COVID19 case.Results and conclusionsThe number of patients treated with radiotherapy during the study period decreased due to precautionary measures. After five weeks, the number of radiotherapy treatments began to increase. Just over half of the radiotherapy patients (53.5%) treated at the GPCC reside in the city of Poznan or in one of the ten surrounding counties where COVID19 incidence was low and reached at the end of the study period cumulative number of cases n = 204. The precautionary measures were effective qRT-PCR tests were performed in 1545 individuals (patients and hospital staff) revealing four staff members and none patient with a positive PCR result. Immunoglobulin testing was performed in 1132 individuals (patients and hospital staff). A total of 63 individuals were positive for antibodies

Occurrence of ocular melanoma thirteen years after skin melanoma: two separate primaries or metastatic disease? A case solved with NRAS and CDKN2A (INK4A-ARF) mutational analysis.

Contains fulltext : 71272.pdf (publisher's version ) (Closed access)The differential diagnosis between primary uveal melanoma and cutaneous melanoma metastasis in the eye may be difficult, both clinically and histologically. We report successful application of combined mutational analysis of the NRAS and the CDKN2A gene to discriminate between these two entities. The patient had a history of a superficial spreading cutaneous melanoma of the left shoulder. Nine years later, she developed a lymph node metastasis in the left axilla, and 13 years later she presented with an atypical, pigmented tumor in the uvea. Histologically, the origin of the uveal melanoma could not be determined with certainty. We performed molecular analysis on the skin melanoma, the lymph node metastasis and the uveal melanoma. We detected an NRAS codon 61 mutation (c.182A>G, p.Gln61Arg) in all three tumor specimens. This mutation was absent in the normal control tissue of the patient, thereby excluding a germline mutation. To confirm a clonal relationship between the tumors, we also performed CDKN2A mutational analysis. We detected a CDKN2A mutation ((p16) c.238C>T, p.Arg80X, (p14) c.404C>T, p.Pro135Leu)) in the tumor samples, but not in the normal control tissue of the patient. We concluded that the uveal melanoma is a metastasis from the cutaneous melanoma removed 13 years before