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Objective Premature ovarian insufficiency is a lack of ovarian functions in patients younger than 40 years old. Genetic causes leading to accelerated follicle depletion may result in premature ovarian insufficiency. We aimed to determine genetic etiology of nonsyndromic premature ovarian insufficiency cases from Turkey. Materials and methods We analyzed 86 nonsyndromic premature ovarian insufficiency cases and 26 matched control female participants. Participants have been investigated in cytogenetic analysis followed by FMR1 repeat size expansions and search of variants for nine premature ovarian insufficiency-associated genes. Results Four cases had a structural cytogenetic abnormality. Two cases revealed with premutation size FMR1 triplet repeat expansion. Four cases carried variants in which two were very rare in FSHR and PDPK1, and three were novel in NR5A1, PDPK1, and POF1B genes. Six novel variants have been identified in NOBOX, NR5A1, POF1B, and PDPK1 in control population assigned to be benign alterations. Conclusion Mosaicism of sex chromosomes was responsible in 4.6% and FMR1 premutation in 2.4% of premature ovarian insufficiency cases, while the association of premature ovarian insufficiency-related genes was found very subtle. Novel variants in NR5A1, PDPK1, and POF1B may necessitate further evaluation for their association with premature ovarian insufficiency via functional studies.

Introduction A meta-analysis of three large randomized trials has demonstrated that len maint prolongs progression free survival (PFS) and overall survival (OS) in pts with MM who have undergone ASCT. While len maint benefits pts with both high-risk and standard-risk cytogenetics, it does not appear to provide equal magnitude of benefit to patients with high-risk cytogenetics. We conducted a retrospective analysis comparing the outcomes of pts with MM who underwent ASCT at our institution and len maint compared to no maint. We further evaluated the impact of len maint on the two cytogenetic groups. Methods We performed a retrospective analysis of 1002 consecutive pts with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received including maint, and clinical outcomes. Pts were excluded from the analysis if they received len combination or other drug maint therapies. High-risk cytogenetics was defined as having t(4;14), t(14;16), gain 1q, or del17p. PFS and OS were estimated using Kaplan-Meier method. Log-rank test was used to compare PFS and OS between the groups and Cox proportional hazard models were used to estimate the hazard ratios (HR). Results Pt characteristics are listed in Table 1. 484 pts (53.3%) received no maint while 423 pts (46.7%) received len maint. 245 pts (24.4%) had high-risk cytogenetics while 561 pts (56%) had standard-risk cytogenetics with the remaining unknown. Both PFS and OS were significantly better in the len maint group compared to the no maint group (Figure 1). Adjusting for pts age at transplant, cytogenetic risk, pre-transplant and post-transplant disease status, and ISS staging, the superiority in PFS and OS remained statistically significant, HR=0.50 (95% CI: 0.41-0.62), p Conclusion Consistent with previously published data, our results demonstrate an improvement in outcomes in MM pts treated with len maint following ASCT compared to no maint regardless of cytogenetic risk group. Larger studies are needed to assess the individual benefit obtained with len maint with each high-risk cytogenetic abnormality. Several trials incorporating newer drugs with novel mechanisms of action are currently being done that could further optimize maint therapy and lead to better outcomes in high-risk group.

Pure distal monosomy of the long arm of chromosome 10 is a rare cytogenetic abnormality. The location and size of the deletions described in this region are variable. Nevertheless, the patients share characteristic facial appearance, variable cognitive impairment and neurobehavioral manifestations. A Minimal Critical Region corresponding to a 600 kb Smallest Region of deletion Overlap (SRO) has been proposed. In this report, we describe four patients with a distal 10q26 deletion, who displayed attention-deficit/hyperactivity disorders (ADHD). One of them had a marked behavioral profile and relatively preserved cognitive functions. Interestingly, the SRO was not included in the deleted segment of this patient suggesting that this deletion could contain candidate genes involved in the control of neurobehavioral functions. One of these candidates was the CALY gene, known for its association with ADHD patients and whose expression level was shown to be correlated with neurobehavioral disturbances in varying animal models. This report emphasizes the importance of the behavioral problems as a cardinal feature of the 10q microdeletion syndrome. Haploinsufficiency of CALY could play a crucial role in the development of the behavioral troubles within these patients.

Monosomy 7 and/or deletion of the long arm of chromosome 7 is a common cytogenetic aberration in children with myelodysplastic syndrome (MDS) and is associated with poor outcome. In this report, we present an unusual cytogenetic abnormality leading to loss of both the whole short and whole long arms of chromosome 7, which was found in the bone marrow cells of three pediatric patients with MDS. Using a combination of conventional and molecular cytogenetic methods, a tiny "dot-like" marker chromosome was found and described as der(7)del(7)(p11)del(7)(q11). Together with one previously published case, this chromosomal aberration represents a new rare recurrent karyotypic abnormality involving chromosome 7 in children with MDS.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma characterized by distinctive, large, and bizarre Reed–Sternberg–like cells associated with an intense inflammatory infiltrate. The biology of MIFS is still poorly understood, and only two previous cases had been studied cytogenetically. In the present case, analysis of MIFS in the foot of a 53-year-old man revealed the chromosome translocation t(2;6)(q31;p21.3) as the only cytogenetic abnormality. This finding is distinct from the two cases previously reported. Additional studies are needed to verify whether any of these chromosome rearrangements are involved recurrently in MIFS.

We describe a patient with acute leukemia of ambiguous lineage who had trisomy 4 as the sole cytogenetic abnormality. Clinical, pathological, immunophenotypic and molecular features are presented and compared with the previous 4 published cases. Over expression of c-kit, which is localized to chromosome 4, was documented on the leukemic blasts. Prognosis seems to be poor. Treatment with acute lymphoblastic leukemia like regimens seems to be superior compared to acute myeloid leukemia like regimens and allogeneic stem cell transplant is recommended after achieving remission., Highlights • Acute leukemia of ambiguous lineage with trisomy 4 as the sole abnormality is a rare disease. • Clinical and pathological details of a case are presented and compared with prior 4 published cases. • Over expression of c-kit, localized to chromosome 4, may play a pathogenic role in this disease. • Prognosis seems to be poor. • Treatment with ALL like regimens seems to be superior compared to AML like regimens.

Mesenchymal chondrosarcoma is a rare malignant tumor that comprises about 3-10% of all sarcomas. Reports of cytogenetic studies of mesenchymal chondrosarcoma are limited and no consistent cytogenetic abnormality has surfaced. Some mesenchymal chondrosarcomas have a t(11;22) translocation suggesting a relationship with the PNET/Ewing tumor family. We report what to our knowledge is the first case of trisomy 8 as the sole cytogenetic abnormality in a mesenchymal chondrosarcoma.

A clear cell sarcoma from the kidney of a 12-month-old male child manifested a balanced translocation, t(10;17)(q22;p13). This is the second report of this cytogenetic abnormality in renal clear cell sarcoma.

Cytogenetic abnormalities have been described in a number of solid tumours of childhood. In many paediatric sarcomas and lymphomas, the demonstration of specific translocations has led to the identification of fusion genes of diagnostic, prognostic and potential therapeutic importance. These characteristic translocations are frequently accompanied by secondary karyotypic changes that may contribute to neoplastic progression. In paediatric solid tumours where no primary cytogenetic abnormality has been identified, numerous recurring aberrations are observed that often correlate with prognosis. In this review, karyotypic abnormalities detected by both conventional and recent molecular cytogenetic approaches in the most common solid tumours of childhood — neuroblastoma, Wilms' tumour, rhabdomyosarcoma, Ewing's tumour and certain lymphomas — are described. Characterization of these aberrations will not only increase our understanding of tumourigenesis, but will also provide unique diagnostic and prognostic markers for the clinic.

Conventional cytogenetic techniques are the standard for the diagnosis and follow-up of patients with AML and ALL. Some characteristic translocations associated with various groups of AML diagnoses, such as t(8;21), t(15;17), and inv(16) for M2, M3, and M4eo, respectively, have been recognized for years. The most common cytogenetic abnormality found in childhood ALL and hyperdiploid adult ALL is t(9;22). Future directions include increased use of FISH and molecular diagnostic techniques. The clinical cytogenetics laboratory plays a major role in the diagnosis and management of AML and ALL.

We report a case of pre-B acute lymphoblastic leukaemia with an unusual translocation between chromosome 3 and 9, with del(10p12) [13]. The diagnosis at presentation was made by the morphology, cytochemistry and immunophenotyping. Cytogenetic analysis was also done at presentation. To the best of our knowledge and after literature search this appears to be a rare cytogenetic abnormality in ALL.

Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two notable cases are described: (1) a case of bilateral Wilms tumor in which only the left-sided tumor contained isochromosome 7q and (2) a case of left-sided Wilms tumor in which the tumor contained isochromosome 7q, in addition to four other chromosomal abnormalities associated with Wilms tumor.

Congenital leukemia occurring within 4 weeks of birth is extremely rare and, excluding transient neonatal myeloproliferation associated with Down syndrome, makes up approximately 1% of childhood leukemias. It is usually seen as acute myeloid leukemia (AML), most frequently French–American–British (FAB) types M4 and M5. Recurrent cytogenetic abnormalities have been reported in this group, and in approximately one third of cases the MLL gene at 11q23 is involved. These patients generally have a poor prognosis. We present a case of congenital leukemia (AML FAB type M1) with an acquired translocation between chromosomes 6 and 17.

We report the occurrence of an unbalanced whole-arm translocation of der(8;17)(q10;q10) in an 80-year-old female patient with Waldenström macroglobulinemia. To our knowledge, der(8;17)(q10;q10) has not been described in Waldenström macroglobulinemia. Although this cytogenetic abnormality has been reported in a number of solid tumors, a literature review suggests also a possible association with B-cell chronic lymphoproliferative disorders.

We describe a case of a patient affected by a chronic myeloproliferative disorder with t(8;21)(q22;q22) and trisomy 8 at diagnosis. At the time of blastic metamorphosis, 2 months later, trisomy 8 metaphases were significantly reduced, while a predominance of t(8;21) was present. Finally, in the phase of leukemic regrowth following chemotherapy administration, monosomy 8 associated with der(21)t(8;21) was the predominant cytogenetic abnormality.

Summary The term mantle cell lymphoma (MCL) has been introduced recently, to describelymphomas related to the primary B follicle and the mantle of the secondary lymphoid follicle. MCL forms a subset of diffuse small cleaved cell lymphomas according to the Working Formulation and correspond closely to the centrocytic lymphomas described in the Kiel classification. They form a distinct clinico-pathological entity and are associated with a specific cytogenetic abnormality; the t(11;14)(g13;q32), which can be detected at a molecular level by rearrangement of the bcl -1 oncogene. As diagnostic criteria for MCL have now been precisely outlined and the clinical presentation described, it should be possible in the future to develop rational treatment protocols for this group of patients, who have a notoriously poor prognosis.

We report the results of cytogenetic analysis of a case of unicameral bone cyst with a t(16;20(p11.2;q13) present as the sole abnormality. To our knowledge, this is only the second report of a cytogenetically characterized tumor of this type.

We describe two cases of rhabdomyosarcoma with a translocation involving 12q13 as the primary cytogenetic abnormality. Literature review of 35 cases has identified 3 other cases with this abnormality, and we speculate that this may be another nonrandom rearrangement in rhabdomyosarcoma.

We describe a case of pediatric acute lymphoblastic leukemia (ALL) with trisomy 5 as a sole cytogenetic abnormality. A comparison is made with the two cases of adult acute lymphoblastic leukemia with trisomy 5 in the literature. This rare cytogenetic abnormality may portend an especially poor prognosis in patients with ALL.

Trisomy 10 is a rare nonrandom cytogenetic abnormality found in association with acute myeloid leukemia (AML). The hematological and clinical features associated with this finding have not yet been clearly defined. A literature review revealed 13 cases of trisomy 10 in AML, some reported as a minority component of a more comprehensive AML study and therefore lacking a full description of both clinical and hematological features. We present a summary of these reports and add three new cases to the literature.

A case of acute leukemia has two distinct immature blast lines, lineage inconsistency with CD 4 positivity, and trisomy 13q as the effective cytogenetic abnormality. This case represents another instance of trisomy 13 with acute leukemia developing in a more primitive pluripotent stem cell.

We report two cases of leiomyomas of the uterus with a deletion of the long arm of chromosome 13. To our knowledge this cytogenetic abnormality as a single change has not been reported previously. One of our cases showed a del(13)(q14q32) and the other a del(13)(q13q33). We discuss the cases and compare our findings with previous ones reported in the literature.

A case with an atypical myeloproliferative disorder (MPD) characterized by overt dysmyelopoiesis, mostly represented by abnormal thrombopoiesis and showing a t(3;18)(q21;q21), is described. The unusual hematological findings, which characterized a disease borderline between two distinct entities, namely MPD and myelodysplastic syndromes, are also discussed in relation to the cytogenetic abnormality affecting region 3q21 and possibly dictating the abnormal thrombopoiesis.

We report the first case of pentasomy of chromosome 8 as the sole cytogenetic abnormality in the bone marrow of a patient with chronic myelomonocytic leukemia, together with a review of the literature describing polysomy of chromosome 8 in hematological malignancies.

Clonal chromosomal aberrations are reported in about 25% of the patients with hairy cell leukemia (HCL). No consistent cytogenetic abnormality has been described in HCL; most of the chromosomal changes found have been deletions and inversions, with the rare occurrence of translocations. While most of the chromosomal aberrations in HCL are common to the ones found in B cell chronic lymphocytic leukemia and other B cell lymphoproliferative disorders, there are also certain chromosomal changes that are not found in other B cell lymphoproliferative disorders. We present here a 63-year-old male patient with hairy cell leukemia with the clonal del(17)(q25), which has nor previously been reported in HCL. (C) Elsevier Science Inc., 1998.

Cytogenetic analysis of bone marow cells from a 53-year-old man with acute nonlymphocytic leukemia (FAB-M4) revealed a t(2;14)(q23;q32.3) as the sole cytogenetic abnormality. This is the first report of a t(2;14)(q23;q32.3) as the sole abnormality in acute nonlymphocytic leukemia (M-4). The findings are discussed in relation to the possible role of genes located at 2q23 in acute nonlymphocytic leukemia.

We present a case of B-cell acute lymphoblastic leukemia (ALL) in whose leukemic cells trisomy 5 (+5) was the only cytogenetic anomaly observed. This is the first report of +5 as the sole cytogenetic abnormality in ALL; two cases (one questionable) of acute nonlymphocytic leukemia with such a change have been reported. The findings are presented in relation to other cases with +5 as part of a more complicated cytogenetic picture in hematologic disorders.

Cytogenetic analysis of tumor tissue from two patients with medulloblastoma is reported. Both showed the presence of an i(17q) and a der(11)t(8;11)(q11;p11). It is suggested that the t(8;11) may be a translocation associated with medulloblastoma.

Cytogenetic findings obtained from an endometrial adenocarcinoma stage 1A are reported. The primary stem line was pseudodiploid with an abnormal chromosome #8. Three side lines were noted, which collectively involved chromosomes X, #8, #12, and two members of group D. A small percentage of cells was either pseudotetraploid or near-tetraploid. Double minutes were noted in one of the latter cells. Interest in the case is centered on the finding of what appeared to be the primary chromosomal change.

We describe a cytogenetic abnormality with important diagnostic and prognostic implications. The translocation t(1;3)(p36;q21) is an acquired chromosomal rearrangement associated with myelodysplastic syndromes, which have a high propensity for conversion to refractory acute nonlymphocytic leukemia.

Hypereosinophilic syndrome (HES) is a disease process of unknown pathogenesis. Although some cases are believed to be primary hematologic malignancies, this issue remains unsolved. We present a case of HES in whom we have observed a clone of cytogenetically abnormal cells in the bone marrow in parallel with a clinical picture of a hematologic disorder characterized by progressive proliferation and organ infiltration by eosinophils. The cytogenetic abnormality 46,XY,t(7;12)(q11;p11) is previously unreported. Our case, plus other evidence present in the literature, supports the concept that HES is a hematologic malignant neoplasia.