Xianfu Wang

16p13.3 duplication associated with non-syndromic pierre robin sequence with incomplete penetrance

BackgroundPierre Robin sequence (PRS) is a condition present at birth. It is characterized by micrognathia, cleft palate, upper airway obstruction, and feeding problems. Multiple etiologies including genetic defects have been documented in patients with syndromic, non-syndromic, and isolated PRS.Case presentationWe report a 4-year-old boy with a complex small supernumerary marker chromosome (sSMC) who had non-syndromic Pierre Robin sequence (PRS). The complex marker chromosome, der(14)t(14;16)(q11.2;p13.13), was initially identified by routine chromosomal analysis and subsequently characterized by array-comparative genomic hybridization (array CGH) and confirmed by fluorescence in situ hybridization (FISH). Clinical manifestations included micrognathia, U-type cleft palate, bilateral congenital ptosis, upslanted and small eyes, bilateral inguinal hernias, umbilical hernia, bilateral clubfoot, and short fingers and toes. To our best knowledge, this was the first case diagnosed with non-syndromic PRS associated with a complex sSMC, which involved a 3.8 Mb gain in the 14q11.2 region and an 11.8 Mb gain in the 16p13.13-pter region.ConclusionsWe suggest that the duplicated chromosome segment 16p13.3 possibly may be responsible for the phenotypes of our case and also may be a candidate locus of non-syndromic PRS. The duplicated CREBBP gene within chromosome 16p13.3 is associated with incomplete penetrance regarding the mandible development anomalies. Further studies of similar cases are needed to support our findings.

Molecular cytogenetic characterization of undifferentiated embryonal sarcoma of the liver: a case report and literature review

Undifferentiated embryonal sarcoma of the liver (UESL) represents a heterogeneous group of tumors derived from mesenchymal tissues. Earlier cytogenetic studies in limited cases demonstrated that UESL is associated with a recurrent translocation t(11;19)(q11;q13.3-q13.4) or add(19)(q13.4). In this report, we present our array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) findings, and a missense mutation of TP53 gene by DNA sequencing in a 19-year-old patient with UESL. The data were compared to laboratory findings reported by previous studies.

Acquired genomic copy number changes in CML patients with the Philadelphia chromosome (Ph

Chronic myeloid leukemia (CML) is characterized by the BCR-ABL1 fusion gene; this fusion gene is usually a consequence of the Philadelphia (Ph(+)) chromosome, which results from the t(9;22)(q34;q11.2). Patients newly diagnosed with CML are routinely treated with tyrosine kinase inhibitors; however, the clinical course of the disease can vary, and this variance may be associated with genetic heterogeneity. Array comparative genomic hybridization (CGH) technology is a powerful tool for identifying subtle genomic segmental alterations, which can result from either losses or gains of chromosomal material. These changes may reveal the presence of genes that play important roles in disease initiation or progression or in treatment outcomes. To investigate whether subtle somatic copy number changes (CNCs) are commonly present in CML patients, a pilot study of 19 patients with the Ph(+) chromosome, but who were negative for common secondary chromosomal anomalies [+der(22), +8, i(17q), and +19], was conducted using a high-density whole genomic oligonucleotide array CGH analysis. Four of the 19 cases had somatic segmental CNCs, including the loss of 9q34, 15q25.3, and 15q13 and a gain of 7p21.1-p15.3. The findings demonstrate that subtle genomic changes are relatively common in CML patients with a Ph(+) chromosome and that the clinical significance of these findings, especially the newly discovered regions, must be determined in large patient population studies.

A novel t(8;13)(q21;q22) translocation in a pediatric lipoma.

Pediatric lipomas are rare and their etiology is unknown. As in adult lipomas, a segment of 12q13-q15 has been documented as a common chromosomal rearrangement region. Here, we report a pediatric lipoma case without rearrangement of 12q13-q15 but with an apparently balanced translocation involving chromosomes 8 and 13 [t(8;13)(q21;q22)] detected by routine cytogenetic analysis, and small deletions on 5q21.1 and 8q21.11 detected by array comparative genetic hybridization. The small deletion on 8q21.11 is possibly due to chromosomal instability at the breakpoint of the translocation.

An Array-based Comparative Genomic Hybridization Platform for Efficient Detection of Copy Number Variations in Fast Neutron-induced Medicago truncatula Mutants

Mutants are invaluable genetic resources for gene function studies. To generate mutant collections, three types of mutagens can be utilized, including biological such as T-DNA or transposon, chemical such as ethyl methanesulfonate (EMS), or physical such as ionization radiation. The type of mutation observed varies depending on the mutagen used. For ionization radiation induced mutants, mutations include deletion, duplication, or rearrangement. While T-DNA or transposon-based mutagenesis is limited to species that are susceptible to transformation, chemical or physical mutagenesis can be applied to a broad range of species. However, the characterization of mutations derived from chemical or physical mutagenesis traditionally relies on a map-based cloning approach, which is labor intensive and time consuming. Here, we show that a high-density genome array-based comparative genomic hybridization (aCGH) platform can be applied to efficiently detect and characterize copy number variations (CNVs) in mutants derived from fast neutron bombardment (FNB) mutagenesis in Medicago truncatula, a legume species. Whole genome sequence analysis shows that there are more than 50,000 genes or gene models in M. truncatula. At present, FNB-induced mutants in M. truncatula are derived from more than 150,000 M1 lines, representing invaluable genetic resources for functional studies of genes in the genome. The aCGH platform described here is an efficient tool for characterizing FNB-induced mutants in M. truncatula.

Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non–Small Cell Lung Cancer ☆ ☆☆

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) of non-small cell lung carcinoma (NSCLC) have different clinical presentations, morphologies, treatments, and prognoses. Recent studies suggested that fundamental genetic alterations related to carcinogenesis of each tumor type may be different. In this study, we investigated the genomic alterations of 47 primary NSCLC samples (22 ACs and 25 SCCs) as well as the corresponding normal tissue using array comparative genomic hybridization. Frequent copy number alterations (CNAs), which were identified in more than 68% of all of the cases, were evaluated in each subtype (SCC and AC), and a CNA signature was established. Among these CNAs, 37 genes from the SCCs and 15 genes from the ACs were located in a region of gain, and 4 genes from the SCCs and 13 genes from the ACs were located in a region of loss. The most frequent gain was located on 3q26-29 including the gene TP63 in SCCs and 7q11.23 and 7q36.3 in ACs. Moreover, we identified 3 genetically distinct groups (group I [16 SCC] with CNA signature of SCC; group II [7 SCC + 8 AC], which has a genetically distinctive CNA signature from SCC and AC; and group III [2 SCC + 14 AC] with CNA signature of AC) by gene clustering extracted from CNAs, which are associated with a prognosis. The present study contributed to the molecular characterization of AC and SCC of NSCLC and showed a subtype of tumor that has a unique genetic CNA signature. However, further study about the significance of these 3 distinct groups and their usefulness as a diagnostic marker of identified CNAs is necessary.

Characterization of a novel t(2;5;11) in a patient with concurrent AML and CLL: a case report and literature review.

Acute myeloid leukemia (AML) that occurs concurrent with a diagnosis of chronic lymphocytic leukemia (CLL) is rare, but the number of cases recognized has recently dramatically increased as a result of the application of flow cytometry. This raises a series of questions regarding the clinical characterization of mixed leukemia, whether this diagnosis possesses unique cytogenetic abnormalities, and the possible association between AML and CLL cell clones. The current study attempts to answer these questions by evaluating an 80-year-old man with concurrent diagnoses of AML-M0 and CLL. Routine G-banded chromosome, array based comparative genomic hybridization, and fluorescence in situ hybridization analyses were used to characterize complex chromosomal rearrangements in the patients bone marrow. Novel complex translocations involving chromosomes 2, 5, and 11, as well as submicroscopic deletions and duplications, were revealed. This case study reports a t(2;5;11) in either AML-M0 or in CLL by using array based comparative genomic hybridization and fluorescence in situ hybridization analyses to facilitate the diagnosis. The study also delineates the clinical characteristics and cytogenetic changes that occur with concurrent AML and CLL.

Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ hybridization in a patient with acute promyelocytic leukemia: A case report and literature review.

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The current study presents the case of a 54-year-old female with APL carrying the atypical PML/RARA fusion signal due to a novel complex variant translocation t(15;16;17)(q22;q24;q21), as well as the classical PML/RARA fusion signal. Subsequent array comparative genomic hybridization revealed somatic, cryptic deletions on 3p25.3, 8q23.1 and 12p13.2-p13.1, and a duplication on 8q11.2; however, no genetic material loss or gain was observed in the breakpoint regions of chromosomes 15, 16 or 17. To the best of our knowledge, this is the first report of the coexistence of two abnormal clones, one classical and one variant, presenting simultaneously in addition to cryptic chromosome segmental imbalances in an adult APL patient.

Coexistence of t(2;14;11)(p16.1;q32;q23) and t(14;19)(q32;q13.3) chromosome translocations in a patient with chronic lymphocytic leukemia: A case report

Rationale: With combination of multiple techniques, we have successfully characterized unique, complex chromosomal changes in a patient with chronic lymphocytic leukemia (CLL), a lymphoproliferative disorder. Diagnoses: The diagnosis was based on white blood cell, flow cytometry, and immunophenotypes and confirmed by karyotype, fluorescence in situ hybridization, and array comparative genomic hybridization from the patients blood culture. Interventions: The patient was given fludarabine, cyclophosphamide and rituximab (FCR) for 6 cycles. Outcomes: After completion of 6 cycles of FCR, the computed tomography scans of the neck/chest/abdomen/pelvic showed that the patient in CR. During the 10-month follow-up, the patients clinical course remained uneventful. Lessons: The translocation t(14;19) identified in this patient is a recurrent translocation found in patients with chronic B-cell lymphoproliferative disorders and the 3-way translocation involving chromosomes 2, 14, and 11 may play a role as an enhancer.

Clinical report: variable phenotypic expression in a large sibling cohort with a deletion of 4p16.1

We report a half‐sibling cohort with deletion of 4p16.1, astigmatism, gross and fine motor delay, variable intellectual disability, and variable behavioral concerns. However, two siblings without the deletion also had learning delays and psychological concerns. Thus, variable phenotypic expression was seen and the significance of deletion of 4p16.1 remains unclear.