Trichorhinophalangeal syndrome type 1; transcriptional repressor GATA binding 1 (TRPS1), a member of the GATA transcription factor family, functions primarily as a transcriptional repressor. TRPS1 is frequently utilised as a diagnostic marker for breast carcinoma, although its specificity is lower than previously believed. Moreover, TRPS1 is expressed in various solid tumours originating from the skin, salivary glands, soft tissues, prostate, urothelium, and female genital tract. The current study evaluated the diagnostic and prognostic significance of TRPS1 in 451 primary tubo-ovarian tumours. The cohort included 94 high-grade serous carcinomas (HGSCs), 81 low-grade serous carcinomas (LGSCs), 31 micropapillary serous borderline tumours (mSBTs), 92 clear cell carcinomas (CCCs), 52 endometrioid carcinomas (ECs), 31 mucinous carcinomas (MCs), and 70 mucinous borderline tumours (MBTs). Immunohistochemical analysis was performed using tissue microarrays following standardised protocols. Clinical data were analysed to determine the prognostic relevance of TRPS1 expression. TRPS1 expression was detected in 47% of HGSCs, 44% of ECs, 35% of CCCs, 19% of LGSCs, and 29% of mSBTs with complete negativity in MC/MBT. TRPS1-negative HGSC cases had higher recurrence rates than those with positive staining. Furthermore, TRPS1 expression significantly correlated with improved metastasis-free survival in HGSC cases. These findings suggest that TRPS1 may serve as an independent prognostic marker for HGSC. Despite varying expression rates across primary tubo-ovarian carcinomas, the routine use of TRPS1 in the differential diagnosis seems to be limited, as other robust immunohistochemical markers are available for distinguishing the individual subgroups. Further research is needed to clarify the specific functions and clinical implications of TRPS1 in tubo-ovarian cancer.
- Klíčová slova
- HGSC, IHC, TRPS1, high-grade serous carcinoma, immunohistochemistry, tubo-ovarian tumours,
- Publikační typ
- časopisecké články MeSH
Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Most patients with EP-SCNC have metastatic disease upon presentation, and their average overall survival (OS) is less than 12 months. Our study aimed to conduct a complex analysis of EP-SCNC. One hundred eighty-one EP-SCNC tissue samples were subjected to a complex analysis. One hundred fifty-five tumors were pure EP-SCNC, whereas 26 were combined tumors. Immunohistochemistry for ASCL1, NEUROD1, YAP1, POU2F3, Rb1, p53, cyclin D1, p16, PTEN, DLL3, PD-L1, CD56, synaptophysin, chromogranin A, and INSM1 was performed, and 128 samples were analyzed molecularly using next-generation sequencing, comprising DNA and RNA analyses. Detailed results on immunohistochemical and molecular analyses were provided for each primary origin of EP-SCNC separately. Median survival for the whole cohort of patients was 8.94 months. Patient age (≥70 years), tumor mutational burden <15, and TP53 and BRCA2 mutations were negative prognostic factors. High expression of ASCL-1 was associated with shorter OS, whereas high expression of YAP1 was associated with longer OS. Patients with genitourinary tumors had significantly better OS than those with gastrointestinal tract EP-SCNC tumors. Rb1 expression loss was detected more often in genitourinary tract SCNCs. In contrast, p16 overexpression was found more often in genitourinary tract SCNCs. POU2F3 expression was detected more often in combined tumors, whereas NEUROD1 was detected more often in pure EP-SCNC. Regarding "druggable markers," DLL3 was expressed in 66% of tumors and PD-L1 in 17.4%. Detailed analyses of different prognostic and predictive markers are needed to better understand EP-SCNC biology and create more personalized therapy to improve patient prognosis.
- Klíčová slova
- POU class 2 homeobox 3, achaete-scute homolog 1, extrapulmonary neuroendocrine small cell carcinoma, neurogenic differentiation factor 1, tumor mutation burden, yes-associated protein 1,
- MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- malobuněčný karcinom * genetika patologie klasifikace metabolismus mortalita MeSH
- nádorové biomarkery * genetika metabolismus analýza MeSH
- neuroendokrinní karcinom * genetika patologie klasifikace mortalita metabolismus MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery * MeSH
Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.
- Klíčová slova
- human papillomavirus, next-generation sequencing, penile, squamous cell carcinoma, tumor mutational burden,
- MeSH
- ATM protein genetika MeSH
- dospělí MeSH
- erbB receptory genetika MeSH
- infekce papilomavirem MeSH
- inhibitor p16 cyklin-dependentní kinasy genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory penisu * genetika mortalita patologie virologie MeSH
- prognóza MeSH
- proteiny vázající telomery MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- shelterinový komplex MeSH
- spinocelulární karcinom * genetika mortalita patologie virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ATM protein, human MeSH Prohlížeč
- ATM protein MeSH
- CDKN2A protein, human MeSH Prohlížeč
- EGFR protein, human MeSH Prohlížeč
- erbB receptory MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- nádorové biomarkery * MeSH
- nádorový supresorový protein p53 MeSH
- POT1 protein, human MeSH Prohlížeč
- proteiny vázající telomery MeSH
- shelterinový komplex MeSH
- TP53 protein, human MeSH Prohlížeč
Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.
- Klíčová slova
- DICER1, FOXL2, FOXO1, KMT2D, TERT promoter, adult-type granulosa cell tumor of the ovary,
- MeSH
- dospělí MeSH
- forkhead box protein O1 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * genetika patologie MeSH
- mutace MeSH
- nádor z folikulárních buněk * genetika patologie mortalita MeSH
- nádory vaječníků * genetika patologie mortalita MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protein FOXL2 genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- telomerasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- forkhead box protein O1 MeSH
- FOXL2 protein, human MeSH Prohlížeč
- FOXO1 protein, human MeSH Prohlížeč
- protein FOXL2 MeSH
- telomerasa MeSH
- TERT protein, human MeSH Prohlížeč
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of uncertain lineage and low malignant potential. Most tumors behave in a benign manner, but a subset of UTROSCT exhibit an aggressive clinical course with recurrences and metastases. The recurrent molecular alterations in UTROSCT mostly represent gene fusions involving NCOA1-3. We performed a comprehensive clinicopathological, morphologic, immunohistochemical, and molecular analysis on a cohort of 35 UTROSCT. The tumors exhibited various architectural patterns (diffuse, corded/trabecular, tubular, sertoliform, fascicular, whorled, nested, microfollicular, and pseudoglandular), often in combination. The immunohistochemical analysis confirmed the polyphenotypic immunoprofile, often with coexpression of sex cord-stromal, smooth muscle, and epithelial markers, as well as hormone receptors. Next-generation sequencing RNA analysis revealed recurrent NCOA1-3 gene fusions in 22/32 analyzed cases (69%), including ESR1::NCOA3 (11/22), GREB1::NCOA2 (7/22), ESR1::NCOA2 (3/22), and GREB1::NCOA1 (1/22). Tumor mutation burden was low in all cases. The fusion-positive cases exhibited statistically significant association with whorled architecture, conversely necrosis was associated with fusion-negative status. We did not find a significant relationship between any architectural pattern and GREB1 alterations, but the NCOA2-altered tumors were associated with pseudoglandular architecture. The GREB1-altered cases occurred in older patients and tended to be more often intramural masses compared with ESR1-altered cases. On the contrary, the ESR1-altered cases presented more often like submucosal or polypoid tumors. Two tumors exhibited aggressive behavior with recurrent disease. Both of these cases harbored a GREB1::NCOA2 fusion. Unsupervised hierarchical cluster analysis of our cohort revealed 2 main clusters. The tumors with GREB1 or NCOA2 fusion cluster together, suggesting that there are underlying molecular differences between these cases and cases with ESR1::NCOA3 fusion or without fusion. Our findings contribute to the growing knowledge about a rare neoplasm with currently uncertain biological behavior.
- Klíčová slova
- ESR1, GREB1, NCOA1-3, UTROSCT, expression profiling, immunohistochemistry, molecular testing, uterine tumor resembling ovarian sex cord tumors,
- MeSH
- dospělí MeSH
- gonadální stromální nádory * genetika patologie MeSH
- imunohistochemie * MeSH
- koaktivátor 2 jaderných receptorů genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové biomarkery * genetika analýza MeSH
- nádory dělohy * genetika patologie MeSH
- nádory vaječníků genetika patologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- koaktivátor 2 jaderných receptorů MeSH
- nádorové biomarkery * MeSH
- NCOA2 protein, human MeSH Prohlížeč
This study provides an analysis of 37 ovarian Sertoli-Leydig cell tumors (SLCT), focusing on their morphological, immunohistochemical, and molecular features. The cohort was comprised of 9 well-differentiated, 25 moderately differentiated, and 3 poorly differentiated tumors. The immunohistochemical analysis was performed with 28 markers, including diagnostic markers and markers with possible predictive significance. The results showed high expression of sex cord markers (FOXL2, SF1, inhibin A, CD99, calretinin, ER, PR, AR), and variable expression of other markers such as CKAE1/3 (83%), CAIX (14%), and MUC4 (1%). Loss of PTEN expression was present in 14% of cases, and CTLA4 expression was seen in 43% of cases. All tumors were MMR proficient and HER2 and PD-L1 negative. The molecular analysis showed DICER1 mutations in 54.5% of cases, and a FOXL2 mutation in 6% of tumors. In addition, we detected 2 cases with TERT promoter mutation. RNA NGS sequencing identified significant differences in mRNA expression between DICER1MUT and DICER1WT tumors. The DICER1WT tumors showed increased expression of PRKCA, HNF1A, LDLR, and MAP2K5. On the contrary, the DICER1MUT cases showed increased expression of CDK6, NOTCH2, and FGFR2. The results of our study show that SLCTs exhibit distinct molecular features based on their degree of differentiation. We have confirmed that DICER1 mutations are characteristic of moderately and poorly differentiated SLCTs, while well-differentiated SLCTs may represent a distinct entity. DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.
- Klíčová slova
- DICER1, Immunohistochemistry, MRNA expression, Ovarian tumors, Sertoli–Leydig cell tumor, Sex cord-stromal tumor,
- Publikační typ
- časopisecké články MeSH
The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the "diagnostic" antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells.
- Klíčová slova
- Granulosa cell tumors, Immunohistochemistry, Ovarian tumors, Sex cord-stromal tumors,
- MeSH
- dospělí MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádor z folikulárních buněk * patologie metabolismus MeSH
- nádorové biomarkery * analýza MeSH
- nádory vaječníků * patologie metabolismus diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery * MeSH
BACKGROUND: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. METHODS: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. RESULTS: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. CONCLUSION: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.
- Klíčová slova
- Immunohistochemistry, Ovarian tumors, Ovary, Sex cord-stromal tumors, Stathmin,
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- gonadální stromální nádory * patologie diagnóza metabolismus terapie MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * analýza MeSH
- nádory vaječníků * patologie diagnóza metabolismus terapie MeSH
- prognóza MeSH
- stathmin * analýza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery * MeSH
- stathmin * MeSH
- STMN1 protein, human MeSH Prohlížeč
Low-grade serous carcinoma (LGSC) may develop from serous borderline tumor (SBT) tissue, where the micropapillary type (mSBT) presents the highest risk for progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches, including targeted treatment, are needed. However, knowledge about the molecular landscape of LGSC and mSBT is limited. A sample set of 137 pathologically well-defined cases (LGSC, 97; mSBT, 40) was analyzed using capture DNA next-generation sequencing (727 genes) and RNA next-generation sequencing (147 genes) to show the landscape of somatic mutations, gene fusions, expression pattern, and prognostic and predictive relevance. Class 4/5 mutations in the main driver genes (KRAS, BRAF, NRAS, ERBB2, USP9X) were detected in 48% (14/29) of mSBT cases and 63% (47/75) of LGSC cases. The USP9X mutation was detected in only 17% of LGSC cases. RNA next-generation sequencing revealed gene fusions in 6 of 64 LGSC cases (9%) and 2 of 33 mSBT cases (9%), and a heterogeneous expression profile across LGSC and mSBT. No molecular characteristics were associated with greater survival. The somatic genomic and transcriptomic profiles of 35 mSBT and 85 LGSC cases are compared for the first time. Candidate oncogenic gene fusions involving BRAF, FGFR2, or NF1 as a fusion partner were identified. Molecular testing of LGSC may be used in clinical practice to reveal therapeutically significant targets.
- MeSH
- azosloučeniny * MeSH
- genomika MeSH
- lidé MeSH
- mutace MeSH
- nádory vaječníků * diagnóza genetika MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- RNA MeSH
- serózní cystadenokarcinom * diagnóza genetika MeSH
- stanovení celkové genové exprese MeSH
- stupeň nádoru MeSH
- thiolesterasa ubikvitinu genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- azosloučeniny * MeSH
- Martius scarlet blue trichrome MeSH Prohlížeč
- protoonkogenní proteiny B-Raf MeSH
- RNA MeSH
- thiolesterasa ubikvitinu MeSH
- USP9X protein, human MeSH Prohlížeč
Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method. Except for high-grade serous carcinoma, we correlated the findings of IHC and PCR with NGS-based MSI testing. We compared the results with somatic and germline mutation in MMR genes. Among the whole cohort, seven MMR-D cases, all clear cell carcinomas (CCC), were found. On PCR analysis, 6 cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in 2 cases, the mutation was germline (Lynch syndrome). An additional 5 cases with a mutation in MMR gene(s) with MSS status and without MMR-D were identified. We further utilized sequence capture NGS for MSI testing. Employing 53 microsatellite loci provided high sensitivity and specificity. Our study shows that MSI occurs in 7% of CCC while it is rare or absent in other nonendometrioid ovarian neoplasms. Lynch syndrome was present in 2% of patients with CCC. However, some cases with MSH6 mutation can evade all testing methods, including IHC, PCR, and NGS-MSI.
- MeSH
- dědičné nádorové syndromy MeSH
- dědičné nepolypózní kolorektální nádory * genetika patologie MeSH
- imunohistochemie MeSH
- kolorektální nádory MeSH
- lidé MeSH
- mikrosatelitní nestabilita MeSH
- mutace MeSH
- nádory glandulární a epitelové * MeSH
- nádory mozku MeSH
- oprava chybného párování bází DNA genetika MeSH
- polymerázová řetězová reakce MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH