INTRODUCTION: Among patients with Acute Myeloid Leukemia (AML), the karyotype at diagnosis is an important prognostic indicator for predicting outcomes. Several studies have been done to identify the most common cytogenetic abnormalities seen in patients in other countries, however, limited studies have been done in our setting. OBJECTIVE: The study aims to determine the most common abnormalities present among patients with AML referred for Fluorescence in situ Hybridization (FISH) at the National Kidney and Transplant Institute. METHODOLOGY: The study included 131 adult patients with a mean age o 46. Fluorescence in situ Hybridization was used to identify the following cytogenetic abnormalities: t(8;21), 11q23 (MLL), 16q22 (CBFB-MYH11), t(15;17) (PML/RARA), t(9;22) (BCR/ABL), 7q31 deletion, and Monosomy 7. RESULTS: FISH was negative in 40% (n=53) of patients. 7q31 deletion is the most frequently identified cytogenetic abnormality among patients with a single abnormality (n=17, 13%) present and is the most frequently identified abnormality among patients with multiple abnormalities (n=26). 7q31 deletion is more frequently observed among patients between the ages 51 to 60 years old and among patients with AML with monocytic differentiation. 22% (n=29) of patients have multiple abnormalities, with the most common abnormalities to occur together are 7q31 deletion and t(8;21) (n=20, 15%). Patients with negative results and patients with multiple cytogenetic abnormalities are commonly seen within the 41 to 50 age group. CONCLUSION The current study provides a single-institution view of the cytogenetic abnormalities among adult Filipino patients with AML using FISH. Further investigation on the clinical history of these patients, with correlation with other methods, as well as epidemiologic studies are needed to better understand the similarities and differences seen from previously reported incidences.
acute myeloid leukemia ; fluorescence in situ hybridization ; cytogenetics ; profiling ; hematology ; Filipino

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.
Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; In Situ Hybridization, Fluorescence ; Neoplasm Staging ; Retrospective Studies

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ²=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.
Female ; Pregnancy ; Humans ; Retrospective Studies ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Aneuploidy ; Prenatal Diagnosis/methods* ; Sex Chromosome Aberrations ; Sex Chromosomes/genetics*

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.
Child ; Adolescent ; Humans ; Male ; Female ; Lymphoma, Follicular/pathology* ; Lymphoma, B-Cell/pathology* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Proto-Oncogene Proteins c-bcl-2/genetics*

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ²=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ²=246.72,P<0.001) or C-MET amplification (χ²=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Mutation ; Lung Neoplasms/genetics* ; ErbB Receptors/genetics*

OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; DNA Copy Number Variations ; Placenta ; Chromosomes, Human, Pair 1 ; In Situ Hybridization, Fluorescence ; Prenatal Diagnosis/methods* ; Fetus ; Amniotic Fluid ; Chromosome Aberrations ; Trisomy/genetics*

OBJECTIVE: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). METHODS: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. RESULTS: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. CONCLUSION Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.
Humans ; Male ; Female ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Cryptorchidism ; Hypospadias ; Retrospective Studies ; Quality of Life ; Sex Chromosome Aberrations ; Karyotyping ; Mosaicism ; Disorders of Sex Development/genetics*

OBJECTIVE: To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8. METHODS: Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness. RESULTS: The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3]. CONCLUSION The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
Female ; Pregnancy ; Humans ; Chromosomes, Human, Pair 8/genetics* ; In Situ Hybridization, Fluorescence ; Gene Rearrangement ; Prenatal Diagnosis ; Centromere

OBJECTIVE: To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH). METHODS: The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay. RESULTS: The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46,XX, 46,XY,inv(9)(p12q12), and 47,XY,inv(9)(p12q12)pat,+mar[75]/ 46,XY,inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism. CONCLUSION Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.
Humans ; Child ; Female ; Pregnancy ; Adult ; In Situ Hybridization, Fluorescence ; Mosaicism ; Genetic Techniques ; Amniotic Fluid ; Chromosomes, Human, Pair 4

OBJECTIVE: To explore the clinical and laboratory characteristics of hematological tumors with different types of abnormalities in platelet derived growth factor β (PDGFRβ) gene. METHODS: A retrospective analysis was carried out on 141 patients with abnormal long arm of chromosome 5 (5q) and comprehensive medical history data from Changhai Hospital Affiliated to Naval Medical University from 2009 to 2020, and their clinical data were collected. R-banding technique was used for chromosomal karyotyping analysis for the patient's bone marrow, and fluorescence in situ hybridization (FISH) was used to detect the PDGFRβ gene. The results of detection were divided into the amplification group, deletion group, and translocation group based on FISH signals. The three sets of data column crosstabs were statistically analyzed, and if the sample size was n >= 40 and the expected frequency T for each cell was >= 5, a Pearson test was used to compare the three groups of data. If N < 40 and any of the expected frequency T for each cell was < 5, a Fisher's exact test is used. Should there be a difference in the comparison results between the three sets of data, a Bonferroni method was further used to compare the data. RESULTS: In total 98 patients were detected to have PDGFRβ gene abnormalities with the PDGFRβ probe, which yielded a detection rate of 69.50% (98/141). Among these, 38 cases (38.78%) had PDGFRβ gene amplifications, 57 cases (58.16%) had deletions, and 3 (3.06%) had translocations. Among the 98 cases, 93 were found to have complex karyotypes, including 37 cases from the amplification group (97.37%, 37/38), 55 cases from the deletion group (96.49%, 55/57), and 1 case from the translocation group (33.33%, 1/3). Analysis of three sets of clinical data showed no significant gender preponderance in the groups (P > 0.05). The PDGFRβ deletion group was mainly associated with myeloid tumors, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (P < 0.001). The PDGFRβ amplification group was more common in lymphoid tumors, such as multiple myeloma (MM) (P < 0.001). The PDGFRβ translocation group was also more common in myelodysplastic/myeloproliferative tumors (MDS/MPN). CONCLUSION Tumors with PDGFRβ gene rearrangement may exhibit excessive proliferation of myeloproliferative tumors (MPN) and pathological hematopoietic changes in the MDS, and have typical clinical and hematological characteristics. As a relatively rare type of hematological tumor, in addition to previously described myeloid tumors such as MPN or MDS/MPN, it may also cover lymphoid/plasma cell tumors such as multiple myeloma and non-Hodgkin's lymphoma.
Humans ; Clinical Relevance ; Hematologic Neoplasms/genetics* ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; Myelodysplastic Syndromes ; Retrospective Studies ; Translocation, Genetic