Short Arm Of Chromosome Research Articles

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants.

The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.

Genetic analysis of a large Han Chinese family line with schizoaffective psychosis

To locate the specific susceptibility genes of a high incidence of schizoaffective disease (SAD) with autonomic dominant inheritance, we recruited a family group from Henan Province with a high incidence of SAD, including 19 individuals sampled from five generations.We used a genome-wide high-density SNP chip to perform genotype detection. The LINKAGE package and MENDEL programs were used for. The two-point and multipoint analyses were calculated by Merlin and SimWalk2 software to obtain the nonparametric linkage (NPL) value, corresponding P value, and parameter linkage limit of detection (LOD) value.Genome-wide linkage analysis yielded a significant linkage signal located on the short arm of chromosome 19. In the dominant genetic model, the LOD of the multipoint parametric analysis was 2.5, and the nonparametric analysis was 19.4 (P < 0.00001). Further haploid genotype analysis localized the candidate region in the 19p13.3–13.2 region, beginning at rs178414 and ending at rs11668751 with a physical length of approximately 4.9 Mb. We believe that the genes responsible for SAD are in this region.

Cytogenetics of Four Common Shrub Species of the Mexican Xerophile Scrub in the Mezquital Valley, Hidalgo, Mexico

Chromosomal characteristics of Dasylirion acrotrichum (Asparagaceae), Flourensia resinosa, (Asteraceae), Tecoma stans (Bignoniaceae), and Citharexylum brachyanthum (Verbenaceae), common elements of the Mexican xerophile scrub are recorded for the first time. The spreading and air-drying technique in root meristems allowed for obtaining chromosome preparations. Chromosomal parameters such as the diploid number (2n), karyotype formula (KF), total haploid chromosome length (THL), average chromosome size (AC), and asymmetry index (TF%) of the analyzed species were obtained, except in C. brachyanthum where neither KF nor TF%. The karyotype formulae of D. acrotrichum (13m+6sm), F. resinosa (11m+7sm), and T. stans (14m+3m+1stsat) represent the first cytogenetic records in Mexican populations. Differences in KF, AC, and position of the satellites concerning other previously analyzed cogenerics show that speciation involves changes in the size and shape of the chromosomes. The diploid numbers confirm basic numbers (x) already recorded, but a 2n=104 observed in C. brachyanthum and the same number in C. myrianthum from Brazil could modify x=9 in favor of x=13, consistent with karyological variation in Verbenaceae where hybridization and polyploidy, among other numerical variation mechanisms, play an important role in chromosomal differentiation. The taxa studied showed satellites in the short arms of chromosomes with displaced centromere. These data are taxonomically useful and could be associated in part with the geographic distribution of the species.

Discordant results for ALK based on immunohistochemistry versus fluorescence in situ hybridization in a cohort of patients diagnosed with lung adenocarcinoma

IntroductionAnaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation. MethodsTo investigate the ALK gene status, we performed FISH and IHC assays in 18 lung adenocarcinoma patients, 12 women and 6 men, aged between 29 and 85 years. Paraffin-embedded samples were analyzed in the Pathology Department of the Hospital Universitario San Ignacio. ResultsResults between the two techniques in 5 patients showed discordant patterns, being positive for FISH and negative for IHC. The borderline to define ALK positivity was set at 15%, These results present experimental evidence that the techniques differ in specific situations. ConclusionsOur findings show that it is advisable to investigate the ALK gene status in patients with suspected lung cancer using both FISH and IHC in combination.

Türkiye'ye endemik Squalius cappadocicus Özuluğ and Freyhof, 2011'un sitogenetik özellikleri

In this study, a detailed chromosome analysis of the endemic Cappadocian Chub, Squalius cappadocicus in Melendiz Stream (Aksaray) was performed. The standard Giemsa staining, C-banding (CBG and CB-DAPI), and Ag-NOR technique were applied. The diploid chromosome number was 50; its karyotype formula was 14M + 16Sm + 10St + 10A. Heteromorphic sex chromosomes weren’t detected in the karyotype of the studied specimens. The number of all chromosomal arms (NF) was 90. In the standard C-banded and CB-DAPI karyotype of the species, dark C-bands were observed in the centromeric region of some bi-armed and acrocentric chromosomes, while slightly centromeric or pericentromeric C-bands were detected in some chromosomes. Three different active Ag-NORs, which were hemizygous, were detected in all samples examined. Two of these active NORs were detected in the bi-armed and the other in the acrocentric chromosome short arm. The Ag-NOR number of this species was evaluated as a feature that distinguishes it from other Squalius species in Türkiye.

Permanent Spreading of 1RS.1AL and 1RS.1BL Translocations in Modern Wheat Breeding.

Wheat-rye translocations 1RS.1BL and 1RS.1AL are used in bread wheat breeding worldwide because a short arm of rye chromosome 1 (1RS) when introgressed into the wheat genome confers resistance to diseases, pests and better performance under drought-stress conditions. However, in durum wheat genotypes, these translocations occur only in experimental lines, although their advantages could enhance the potential of this crop. P.P. Lukyanenko National Grain Centre (NGC) has successfully developed commercially competitive cultivars of bread and durum wheat demanded by many agricultural producers in the South of Russia for decades. Here, 94 accessions of bread and 343 accessions of durum wheat, representing lines and cultivars from collection, competitive variety trials and breeding nursery developed at NGC were screened for 1RS using PCR markers and genomic in situ hybridization. The 1RS.1BL and 1RS.1AL translocations were detected in 38 and 6 bread wheat accessions, respectively. None of the durum wheat accessions showed translocation, despite the fact that some of them had 1RS.1BL donors in their pedigree. The absence of translocations in the studied durum wheat germplasm can be caused by the negative selection of 1RS carriers at different stages of the breeding process due to low quality and difficulties in transferring rye chromatin through wheat gametes.

Interrelated effects of chromosome size, mechanics, number, location-orientation and polar ejection force on the spindle accuracy: a 3D computational study.

The search-and-capture model of spindle assembly has been a guiding principle for understanding prometaphase for decades. The computational model presented allows one to address two questions: how rapidly the microtubule-kinetochore connections are made, and how accurate these connections are. In most previous numerical simulations, the model geometry was drastically simplified. Using the CellDynaMo computational platform, we previously introduced a geometrically and mechanically realistic 3D model of the prometaphase mitotic spindle, and used it to evaluate thermal noise and microtubule kinetics effects on the capture of a single chromosome. Here, we systematically investigate how geometry and mechanics affect a spindle assembly's speed and accuracy, including nuanced distinctions between merotelic, mero-amphitelic, and mero-syntelic chromosomes. We find that softening of the centromere spring improves accuracy for short chromosome arms, but accuracy disappears for long chromosome arms. Initial proximity of chromosomes to one spindle pole makes assembly accuracy worse, while initial chromosome orientation matters less. Chromokinesins, added onto flexible chromosome arms, allow modeling of the polar ejection force, improving a spindle assembly's accuracy for a single chromosome. However, spindle space crowding by multiple chromosomes worsens assembly accuracy. Our simulations suggest that the complex microtubule network of the early spindle is key to rapid and accurate assembly.

Cytogenetic Analysis in Patients with Azoospermia

BACKGROUND&#x0D; Azoospermia (the absence of sperm in the semen) significantly amounts to infertility in men (15 % of infertile men). Since genetics plays a huge part in its origin, genetic testing needs to be considered as an important part of early diagnostics when evaluating azoospermic patients. The aim of our study was to determine the genetic cause of azoospermia, to analyze karyograms and the possible presence of Y chromosome microdeletion.&#x0D; METHODS&#x0D; The study included 20 men diagnosed with azoospermia. The oldest male was 50 and the youngest was 24 years old. They were sent for analysis of karyotype and microdeletions of the Y chromosome (AZF region) to the Center for Genetics of the Faculty of Medicine.&#x0D; RESULTS&#x0D; The results of the cytogenetic analysis showed 3/20 (15 %) of abnormal karyotypes. Three patients were identified with two different translocations that were not previously reported. Two brothers were identified with the same translocation between the short arm of chromosome 8 and the long arm of chromosome 17 [46, XY, t(8;17)(p23;q11)], after both of them had failed in-vitro fertilization (IVF). The third patient with chromosomal translocation between the short arm of chromosome 4 and the long arm of chromosome 11 [46, XY, t(4;11)(p16;q13)]. Molecular genetic analysis showed no Y chromosome microdeletion in any of these three cases. However, from the rest of the group, only one patient had Y chromosome microdeletion in the AZFc region (one of the most common causes of genetic azoospermia). His karyotype was normal.&#x0D; CONCLUSIONS&#x0D; Our study confirms that cytogenetic and molecular genetic analysis plays an important role in identifying the cause of azoospermia. Genetic counseling should be provided when these abnormalities are identified before making any future medical decisions.

Wolf-Hirschhorn syndrome revealed by status epilepticus: A case report

A Wolf-Hirschhorn syndrome is a rare chromosomal anomaly, which results from a deletion of the distal portion of the short arm of chromosome 4 (4p-), the diagnosis is based on a clinical picture, easily recognizable in children, confirmed by molecular cytogenetics. We report the case of baby with wolf-Hirschhorn syndrome revealed by status epilepticus.

Chronic myeloid leukaemia in blast phase with t(9;11)(p21;q23), KMT2A::MLLT3 gene fusion

Case: A 51-year-old man presented with lymphadenopathy and increasing fatigue. He had been diagnosed with chronic myeloid leukaemia (CML) seven months earlier and had a suboptimal response to first line nilotinib, failing to achieve MR1 with BCR-ABL1/ABL persistently >10% (IS). A repeat bone marrow examination showed 90% blasts, consistent with CML in blast phase (CML-BP). The blasts showed monoblastic morphology and immunophenotype. Conventional karyotype showed both t(9;22)(q34;q11.2), involving the long arm of chromosome 9, and t(9;11)(p21;q23), involving the short arm of the same derivative chromosome 9. FISH confirmed KMT2A breakapart. A core biopsy of cervical lymph node demonstrated a monoblastic leukaemic infiltrate and BCR-ABL1 mutational analysis did not identify any resistance mutations. Discussion: Progression of CML to accelerated or blast phase is usually accompanied by a series of genomic events including BCR-ABL1 resistance mutations, other somatic mutations and additional cytogenetic abnormalities (ACAs). Common ACAs include extra Philadelphia chromosome, trisomy 8, trisomy 9 and isochromosome 17q. KMT2A rearrangement involving the 11q23 locus are common in de novo or therapy related acute leukaemia (both myeloid and lymphoid), but rarely reported in CML blast phase (<1%). The few reported cases show an aggressive clinical presentation, poor outcomes and poor response to tyrosine kinase inhibitors (TKI).

Nucleotide Sequence and Chromosome Mapping of 5S Ribosomal DNA from the Dojo Loach, Misgurnus anguillicaudatus

There are 2 genetically divergent groups in the dojo loach Misgurnus anguillicaudatus: A and B. Although most wild-type diploids reproduce sexually, clonal diploids (clonal loach) reproduce gynogenetically in certain areas. Clonal loaches produce unreduced isogenic eggs by premeiotic endomitosis, and such diploid eggs develop gynogenetically following activation by the sperm of sympatric wild-type diploids. These clonal loaches have presumably arisen from past hybridization events between 2 different ancestors. The genomic differences between these 2 groups have not been completely elucidated. Thus, new genetic and cytogenetic markers are required to distinguish between these 2 groups. Here, we compared the 5S rDNA region to develop markers for the identification of different dojo loach groups. The nontranscribed sequence (NTS) of the 5S rDNA was highly polymorphic and group-specific. NTSs were found in clades of 2 different groups in clonal loaches. In contrast, we did not find any group-specific sequences in the coding region of the 5S rRNA gene. Sequences were located near the centromere of the short arm of the largest submetacentric chromosomes in groups A and B and clonal loaches. Thus, the 5S rDNA of the dojo loach is conserved at the chromosomal location. Whereas, the sequences of the NTS regions evolved group-specifically in the dojo loach, with the sequences of both groups being conserved in clonal loaches.

EDEM2 is a diagnostic and prognostic biomarker and associated with immune infiltration in glioma: A comprehensive analysis.

Glioma is a highly common pathological brain tumor. Misfolded protein response, which is strongly associated with the growth of cancerous tumors, is mediated by the gene, endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2. However, this gene has not been linked to glioma. To assess the same, we used The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Genotype-Tissue Expression datasets. The gene was overexpressed in gliomas. This overexpression was linked to unfavorable clinical characteristics, such as the World Health Organization grade, isocitrate dehydrogenase mutation, and the combined loss of the short arm chromosome 1 and the long arm of chromosome 19. Quantitative polymerase chain reaction experiments and immunohistochemistry on clinical samples from our institution verified the gene's expression and clinical importance. The Human Protein Atlas website verified the messenger ribonucleic acid expression of the gene in glioma cell lines, and immunohistochemistry verified the presence of its protein. A previous survival study indicated that its high expression is substantially related to a bad prognosis. It was identified as an independent predictor of primary glioma prognosis using multivariate Cox regression analysis. To forecast individual survival, we created a nomogram based on this (concordance-index = 0.847). Additionally, functional annotation demonstrated its major role in the control of the extracellular matrix and immune system. The scratch assay and transwell migration assay confirmed the decreased invasive ability of U251 glioma cells with the gene knockdown. Its increased expression was found to be related to the extent of macrophage infiltration using the CIBERSORT, ESTIMATE, Single-sample Gene Set Enrichment Analysis, and Tumor Immune Single-Cell Hub (TISCH) algorithms. The Tumor Immune Dysfunction and Exclusion algorithm revealed that the gene can accurately predict the response of immunotherapy (area under the receiver operating characteristic curve = 0.857). Further, isocitrate dehydrogenase 1 mutation is typically more frequent when the gene expression is high. Finally, five medicines targeting this gene were discovered utilizing the molecular docking program and drug sensitivity analysis of the RNAactDrug website. Low expression of the gene inhibited glioma cell invasion. Therefore, the gene is helpful for the diagnosis, prognosis, and case-specific immunotherapy of glioma.

RARE CASE PRESENTAETION: VON HIPPLE LINDAU SYNDROME

Introduction: Von Hippel-Lindau syndrome (VHL) is autosomal dominant hereditary syndrome due to germline mutations of the tumor suppressor gene VHL, located on short arm of chromosome 3. 80% have a positive family history and about 20% of cases are de novo. Various multiple benign and malignant tumors occur affecting multiple organ system, central nervous system, kidneys, adrenals, pancreas, and reproductive system. Common manifestations include including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. Confirmation of diagnosis is done by genetic testing in clinically and radiologically suspicious patient. A male patient of Case Report: age 30 years presented with cerebellar symptoms 2 year ago and MRI is done MRI reveal cerebellar and spinal hemangioblastoma. Patient is operated for cerebellar hemagioblastoma and histologically confirmed. On follow up study b/l renal cell carcinoma, pancreatic cyst and neuroendocrine tumor is found. VHL is a disease Conclusion: with no cure. Regular follow-up with necessary to follow the previous lesions and detect any newly developed VHL-associate tumors.

Anaesthetic Considerations for General Anaesthesia in an Adult Patient with Wolf-Hirschhorn Syndrome and Kyphoscoliosis: A Case Report

Wolf-Hirschhorn Syndrome (WHS), also known as Chromosome 4 deletion syndrome, is a rare hereditary disease with a prevalence of 1 in 50,000. It occurs due to the microdeletion of the short arm of chromosome 4, specifically the 4p16.3 domain. Patients with WHS exhibit diverse phenotypes, including growth retardation, developmental delay, congenital heart disease, and convulsions, depending on the amount of deleted genetic material. This case report focuses on a 25-year-old male who was admitted for cataract extraction and posterior chamber intraocular lens implantation. Through gene analysis, the patient was diagnosed with WHS. He exhibited micrognathia, a short neck, kyphoscoliosis, seizure disorder, and mental retardation. Additionally, he had severe kyphoscoliosis, which resulted in restrictive lung disease. These abnormalities posed significant challenges for anaesthetic management. To ensure a successful general anaesthesia, adequate preparedness for difficult airway management was crucial. A thorough cardiovascular and neuromuscular examination was conducted preoperatively to rule out associated anomalies and minimise complications. The patient’s perioperative antiepileptic cover was continued. Extubation proved challenging due to the patient’s mental retardation and restrictive lung disease. This case underscores the importance of effective anaesthetic management for patients with this rare condition undergoing cataract surgery under general anaesthesia.

Cytogenetic Characteristics of Gerbillus dasyurus and Meriones tristrami (Rodentia: Gerbillinae) from Kilis, Turkey: Conventional and C Banded Karyotypes

In this study, diploid chromosome number and constitutive heterochromatin distributions of chromosomes were determined in Gerbillus dasyurus and Meriones tristrami species. The diploid chromosome numbers (2n) and autosomal chromosome arms (NFa) of G. dasyurus and M. tristrami were determined as 2n=60, NFa= 68, and 2n=72, NFa= 73, respectively. It was found that there were differences in autosomal chromosomal arms (NFa) of two different gerbil species, the karyotypes of which were obtained in this study, compared to previously conducted studies in Türkiye. Heteromorphic chromosome pair (submetacentric/acrocentric) was found in the autosomal set of M. tristrami. There was an enlarged heterochromatin block on the short arm of submetacentric chromosome in heteromorphic chromosome pair.

Perspective of Human Leukocyte Antigen testing

Most of the cells in the body have proteins or markers called human leukocyte antigens (HLA). To determine which cells, belong in the body and which do not, the immune system uses HLA. Human leukocyte antigen (HLA) typing is used to match recipients and donors for bone marrow or cord blood transplants. The human major histocompatibility complex (HLA) is located on the short arm of chromosome 6, and it is a complex of genes that encode cell-surface proteins necessary for immune system regulation. It is well known that this human genetic system is the most polymorphic. HLA class I and class II molecules' biological function is to present antigens that have been processed into peptides. HLA was initially just a list of antigens discovered as a result of transplant rejection. HLAs are alloantigen’s that range from person to person due to genetic variance. In essence, every person's immune system is tailored to the distinct HLA and self-proteins produced by that person; when tissues are transferred to another person, however, things go wrong. Individuals almost always have different "banks" of HLAs, which causes transplant rejection because the recipient's immune system mistakes the transplanted tissue for non-self and kills the foreign tissue. HLAs were found as a result of this realization.

Effects of the pathological E200K mutation on human prion protein: A computational screening and molecular dynamics approach.

The human prion protein gene (PRNP) is mapped to the short arm of chromosome 20 (20pter-12). Prion disease is associated with mutations in the prion protein-encoding gene sequence. Earlier studies found that the mutation G127V in the PRNP increases protein stability. In contrast, the mutation E200K, which has the highest mutation rate in the prion protein, causes Creutzfeldt-Jakob disease (CJD) in humans and induces protein aggregation.We aimed to identify the structural mechanisms of E200k and G127V mutations causing CJD.We used a variety of bioinformatic algorithms, including SIFT, PolyPhen, I-Mutant, PhD-SNP, and SNP& GO, to predict the association of the E200K mutation with prion disease. MD simulation is performed, and graphs for root mean square deviation, root mean square fluctuation, radius of gyration, DSSP, principal component analysis, porcupine, and free energy landscapeare generated to confirm and prove the stability of the wild-type and mutant protein structures.The protein is analyzed for aggregation, and the results indicate more fluctuations in the protein structure during the simulation owing to the E200K mutation; however, the G127V mutation makes the protein structure stable against aggregation during the simulation.

Genetically unresolved case of Rauch-Steindl syndrome diagnosed by its wolf-hirschhorn associated DNA methylation episignature.

Wolf-Hirschhorn syndrome (WHS) is caused by deletion of a critical region of the short arm of chromosome 4. Clinical features of WHS include distinct dysmorphic facial features, growth restriction, developmental delay, intellectual disability, epilepsy, and other malformations. The NSD2 gene localizes within this critical region along with several other genes. Pathogenic variants in NSD2 cause Rauch-Steindl (RAUST) syndrome. Clinical features of RAUST syndrome partially overlap with WHS, however epilepsy and the recognizable facial gestalt are not observed. Here, we report a case of a young boy who presented with developmental delay, dysmorphic features and short stature. After negative chromosomal microarray and whole exome sequencing, genomic DNA methylation episignature analysis was performed. Episignatures are sensitive and specific genome-wide DNA methylation patterns associated with a growing number of rare disorders. The patient was positive for the WHS episignature. Reanalysis of the patient's exome data identified a previously undetected frameshift variant in NSD2, leading to a diagnosis of RAUST. This report demonstrates the clinical utility of DNA methylation episignature analysis for unresolved patients, and provides insight into the overlapping pathology between WHS and RAUST as demonstrated by the similarities in their genomic DNA methylation profiles.

Prenatal diagnosis and pregnancy outcomes of 149 fetuses with tetralogy of Fallot accompanied by concomitant cardiac and extracardiac anomalies

Objective: We aimed to analyze the pregnancy outcomes of cases that were diagnosed prenatally with tetralogy of Fallot (TOF) and to investigate its prenatal diagnosis, treatment conditions, and postnatal outcomes. Methods: The clinical information data of a total of 149 fetuses diagnosed with TOF (145 cases were singleton and 4 cases were twins) were collected and reviewed retrospectively between January 2016 and January 2022 at İstanbul Kanuni Sultan Süleyman Training and Research Hospital. Results: Among completely 61,034 pregnancies between these years, 149 fetuses were diagnosed with TOF by fetal prenatal ultrasound imaging with the occurrence rate of about 0.24% (149/61,034), and the average gestational age was 26.13 weeks. Among these cases, 22 cases (14.76%, 22/149) opted for termination of pregnancy. Of these 149 fetuses, a total of 60 (46.30%, 60/149) accepted genetic testing and 11 (7.38%, 11/149) revealed chromosomal disorders with trisomy 21 in 5 cases, trisomy 18 in 1 case, 22q11.2 microdeletion syndrome in 4 cases and abnormality of the short arm of 8th chromosome in 1 case. After delivery, 4 cases were diagnosed with trisomy 21. Pregnancy was continued in a total of 127 fetuses, of which 114 cases resulted in delivery. While 36 cases were delivered by cesarean section, the other 78 cases were delivered vaginally. Thirteen fetuses died during the pregnancy period. Newborns who survived the postpartum period were followed up to 5 years of age for surgery. Among 114 cases, 28 cases died during the postnatal period at different times. Conclusion: The diagnosis of TOF is mainly established with the help of fetal ultrasound in the second trimester. A genetic examination is also necessary after prenatal diagnosis and multidisciplinary work is also important between departments. TOF without genetic disorder can be successfully corrected with surgery after birth.

Molecular correlates of male germ cell tumors with overgrowth of components resembling somatic malignancies

A small subset of male germ cell tumors (GCT) demonstrates overgrowth of histologic components that resemble somatic malignancies (e.g., sarcoma, carcinoma). The presence of so-called “somatic-type” malignancies (SM) in GCT has been associated with chemotherapy-resistance and poor clinical outcomes in prior studies. However, the molecular characteristics of these tumors remain largely undescribed. In this study, we performed a multi-platform molecular analysis of GCTs with SM diagnosed in 36 male patients (primary site: testis, 29 and mediastinum, 7). The most common histologic types of SM were sarcoma and embryonic-type neuroectodermal tumor (ENT, formerly known as “PNET”), present in 61% and 31% of cases, respectively. KRAS and TP53 mutations were identified by DNA sequencing in 28% of cases each, with enrichment of TP53 mutations in mediastinal tumors (86%). Gains in the short arm of chromosome 12 were seen in 91% of cases, likely reflecting the presence of isochromosome 12p. Numerous copy number changes indicative of widespread aneuploidy were found in 94% of cases. Focal homozygous deletions and amplifications were also detected, including MDM2 amplifications in 16% of cases. Sequencing of paired samples in 8 patients revealed similar mutational and copy number profiles in the conventional GCT and SM components. Oncogenic gene fusions were not detected using RNA sequencing of SM components from 9 cases. DNA methylation analysis highlighted the distinct methylation profile of SM components that sets them apart from conventional GCT components. In conclusion, GCT with SM are characterized by widespread aneuploidy, a distinct epigenetic signature and the presence of mutations that are otherwise rare in testicular GCT without SM. The similarity of the mutational and DNA methylation profiles of different histologic types of SM suggests that the identification of SM components could be more important than their precise histologic subclassification, pending confirmation by further studies.