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.

Acute pancreatitis is an acute inflammatory process of the pancreas that is becoming an increasingly common clinical issue. The most frequent underlying etiologies include gallstones and chronic alcohol use, which account for more than two-thirds of cases. We recently experienced a rare case of acute myeloid leukemia (AML) presenting with recurrent acute pancreatitis, which we later discovered was caused by diffusely infiltrating extramedullary sarcoma in the pancreas. Comprehensive analysis of previous cases of AML presenting as acute pancreatitis suggested involvement of cytogenetic alterations in chromosome 16 in its pathogenesis. Further improvement in management of acute pancreatitis is needed, and clinicians should note that this occasionally fatal condition can be the initial and only manifestation of AML. In practice, prompt initiation of intensive chemotherapy is critical for treating such cases of AML-induced acute pancreatitis.

BACKGROUND: Phosphomannomutase 2 deficiency (PMM2-CDG) affects glycosylation pathways such as the N-glycosylation pathway, resulting in loss of function of multiple proteins. This disorder causes multisystem involvement with a high variability among patients. PMM2-CDG is an autosomal recessive disorder, which can be caused by inheriting two pathogenic variants, de novo mutations or uniparental disomy.
METHODS: Our patient presented with multisystem symptoms at an early age including developmental delay, ataxia, and seizures. No diagnosis was obtained till the age of 31 years, when genetic testing was reinitiated. The patient was diagnosed with a complete maternal mixed hetero/isodisomy of chromosome 16, with a homozygous pathogenic PMM2 variant (p.Phe119Leu) causing PMM2-CDG.A literature review revealed eight cases of uniparental disomy as an underlying cause of CDG, four of which are PMM2-CDG.
CONCLUSIONS: Since the incidence of homozygosity for PMM2 variants is rare, we suggest further investigations for every homozygous PMM2-CDG patient where the segregation does not fit. These investigations include testing for UPD or a deletion in one of the two alleles, as this will have an impact on recurrence risk in genetic counseling.

UNASSIGNED: Nearly 9.89% of chromosome 16 consists of segmental duplications, which makes it prone to non-homologous recombination. The present study aimed to investigate the incidence and perinatal characteristics of submicroscopic chromosome 16 aberrations in prenatal diagnosis.
UNASSIGNED: A total of 2,414 consecutive fetuses that underwent prenatal chromosomal microarray analysis (CMA) between January 2016 and December 2018 were reviewed. Submicroscopic anomalies of chromosome 16 accounted for 11.1% (15/134) of all submicroscopic anomalies detected in fetuses with normal karyotype, which was larger than the percentage of anomalies in any other chromosome. The 15 submicroscopic anomalies of chromosome 16 were identified in 14 cases; 12 of them had ultrasound abnormalities. They were classified as pathogenic (N = 7), and variants of uncertain significance (N = 8). Seven fetuses with variants of uncertain significance were ended in live-born, and the remaining were end in pregnancy termination.
UNASSIGNED: Submicroscopic aberrations of chromosome 16 are frequent findings in prenatal diagnosis, which emphasize the challenge of genetic counseling and the value of CMA. Prenatal diagnosis should lead to long-term monitoring of children with such chromosomal abnormalities for better understanding of the phenotype of chromosome 16 microdeletion and microduplication syndromes.

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.

Inv(16)(p13q22) and t(16;16)(p13;q22) are cytogenetic hallmarks of acute myelomonoblastic leukaemia, most of them associated with abnormal bone marrow eosinophils [acute myeloid leukaemia French-American-British classification M4 with eosinophilia (FAB AML-M4Eo)] and a relatively favourable clinical course. They generate a 5\'CBFB-3\'MYH11 fusion gene. However, in a few cases, although RT-PCR identified a CBFB-MYH11 transcript, normal karyotype and/or fluorescent in situ hybridization (FISH) analyses using commercially available probes are found. We identified a 32-year-old woman with AML-M4Eo and normal karyotype and FISH results. Using two libraries of Bacterial Artificial Chromosome clones on 16p13 and 16q22, FISH analyses identified an insertion of 16q22 material in band 16p13, generating a CBFB-MYH11 type A transcript. Although very rare, insertions should be searched for in patients with discordant cytological and cytogenetic features because of the therapeutic consequences. Copyright © 2015 John Wiley & Sons, Ltd.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 16.
METHODS: A 28-year-old woman underwent amniocentesis at 17 weeks of gestation because of abnormal maternal serum screening for Down syndrome. Amniocentesis revealed a karyotype of 47,XY,+mar[5]/46,XY[9]. Parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis of cultured amniocytes revealed a de novo 16% gene dosage increase of 16q11.2-q22.1. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+mar[10]/46,XY[31]. aCGH analysis of uncultured amniocytes revealed a result of arr 16q11.2q22.1 (46,492,626-68,867,969) × 2.20 with a log2 ratio of 0.15 encompassing RPGRIP1L, FTO, SLC6A2, BBS2 and CDH1. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected partial trisomy 16q in 36/137 (26.3%) of uncultured amniocytes. Polymorphic DNA marker analysis on amniocytes and parental bloods excluded uniparental disomy 16. Premature labor occurred at 25 weeks of gestation, and a 585-g male baby without craniofacial dysmorphism was delivered and survived. At age 1½ years, pediatric follow-ups revealed normal psychomotor development, normal body weight, short stature, congenital hypothyroidism, hearing impairment and hypospadias in the neonate, and the peripheral blood had a karyotype of 46,XY in 40 cultured lymphocytes.
CONCLUSIONS: aCGH, interphase FISH and polymorphic DNA marker analyses of uncultured amniocytes are useful for confirmation of prenatally detected mosaic sSMCs at amniocentesis.

Copy number alteration (CNA) of chromosome 16, a frequent genetic event in tumors including hepatocellular carcinoma (HCC), has been associated with HCC etiology of hepatitis B virus (HBV) and with clinical outcomes in multiple types of cancer. This study identified CNAs in chromosome 16 in relation to intrahepatic recurrence of HCC in a population with high HBV prevalence, and further screened for differentially expressed genes in recurrence-related CNAs. Array comparative genomic hybridization and expression arrays were used to detect CNAs and gene expression differences, respectively. The associations between CNAs and intrahepatic recurrence were analyzed on 66 patients, follow-up period of 3-73 months. One hundred and nine cases were further evaluated regarding the differentially expressed genes. Losses at 16q and 16p were detected in 62.1% and 51.5% of the 66 cases, respectively. The most recurrent CNAs (with frequency >20%) were losses at 16p13.3-13.2, 16p13.11, 16q11.2-22.1, 16q22.1, 16q22.2-24.2 and 16q24.2. Of the CNAs, 16q22.1 loss was significantly associated with unfavorable intrahepatic recurrence-free survival (P = 0.025). Multivariate Cox analysis identified 16q22.1 loss as an independent risk factor for intrahepatic recurrence (HR = 2.32, 95% CI = 1.26-4.27). A panel of 21 genes, including TRADD, PSMB10, THAP11, CTCF and ESRP2, were significantly downregulated in HCCs with 16q22.1 loss compared to those without the loss. These results suggest that loss at 16q22.1 was associated with increased risk for intrahepatic recurrence of HCC, at least in the HBV-prevalence population. Multiple downregulated genes correlated with the loss were screened.

dasHPPboard is a novel proteomics-based dashboard that collects and reports the experiments produced by the Spanish Human Proteome Project consortium (SpHPP) and aims to help HPP to map the entire human proteome. We have followed the strategy of analog genomics projects like the Encyclopedia of DNA Elements (ENCODE), which provides a vast amount of data on human cell lines experiments. The dashboard includes results of shotgun and selected reaction monitoring proteomics experiments, post-translational modifications information, as well as proteogenomics studies. We have also processed the transcriptomics data from the ENCODE and Human Body Map (HBM) projects for the identification of specific gene expression patterns in different cell lines and tissues, taking special interest in those genes having little proteomic evidence available (missing proteins). Peptide databases have been built using single nucleotide variants and novel junctions derived from RNA-Seq data that can be used in search engines for sample-specific protein identifications on the same cell lines or tissues. The dasHPPboard has been designed as a tool that can be used to share and visualize a combination of proteomic and transcriptomic data, providing at the same time easy access to resources for proteogenomics analyses. The dasHPPboard can be freely accessed at: http://sphppdashboard.cnb.csic.es.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has recently been established. Herein we report the sixth case of ACD-associated RCC with a sarcomatoid change. The patient was a 77-year-old man who regularly underwent hemodialysis for 14 years due to chronic renal failure resulting from IgA nephropathy. On computed tomography, a large right RCC was observed with contrast enhancement in the arterial phase. A nodular protrusion into the perirenal fat was detected. Right nephrectomy was performed under laparoscopy. Surgically resected specimens revealed a tan-to-yellow tumor (95 × 75 × 55 mm) with a whitish nodule (20 × 15 × 15 mm) invading into the perirenal fat. Histopathologically, the large carcinoma component of the tumor displayed a cribriform or microcystic growth pattern with deposition of oxalate crystals. The whitish nodule corresponded to the sarcomatoid component, and the spindled and pleomorphic tumor cells showed diffuse positivity of p53 on immunohistochemistry. Fluorescence in situ hybridization revealed trisomy of chromosomes 3 and 16 in the carcinoma component, as was expected from the literature. In addition, increased polysomy of these chromosomes was also observed in the sarcomatoid component. This finding may be related to the development of the sarcomatoid component along with the TP53 mutation.