Expression profiling of uterine leiomyomata cytogenetic subgroups reveals distinct signatures in matched myometrium: transcriptional profilingof the t(12;14) and evidence in support of predisposing genetic heterogeneity.

Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, are classified into distinct genetic subgroups based on recurrent chromosome abnormalities. To develop a molecular signature of UL with t(12;14)(q14-q15;q23-q24), we took advantage of the multiple UL arising as independent clonal lesions within a single uterus. We compared genome-wide expression levels of t(12;14) UL to non-t(12;14) UL from each of nine women in a paired analysis, with each sample weighted for the percentage of t(12;14) cells to adjust for mosaicism with normal cells.

Insertion (12;9)(p13;q34q34): a cryptic rearrangement involving ABL1/ETV6 fusion in a patient with Philadelphia-negative chronic myeloid leukemia.

We report a rare cryptic ins(12;9)(p13;q34q34), a chromosomal abnormality involving the ABL1 (9q34) and the ETV6 (alias TEL; 12p13) genes, detectable only by fluorescence in situ hybridization (FISH), in a patient with Philadelphia-negative chronic myeloid leukemia (CML). Using reverse 4',6-diamidino-2-phenylindole banding on metaphase cells, FISH analysis with BCR/ABL dual-fusion and ETV6 break-apart probes showed that a third ABL signal was inserted into 12p, splitting the ETV6 signal into two adjacent signals. CML patients with an ABL1/ETV6 fusion historically have demonstrated a variable and sometimes transient response to treatment with imatinib mesylate, which was also the case in the present patient.

Uterine leiomyomata with deletions of Ip represent a distinct cytogenetic subgroup associated with unusual histologic features.

Cytogenetic analysis of uterine leiomyomata (UL) shows that about 40% of these benign tumors have simple, clonal chromosomal rearrangements. In contrast, their presumed malignant counterpart, leiomyosarcomas (LMSs), typically has complex numerical and structural abnormalities. Several variants of benign uterine smooth-muscle tumors are defined by histologic phenotypes intermediate between typical UL and LMS, and currently, little is known about their cytogenetic and molecular genetic features.

Impact of patient mutations on heterodimer formation and function in human galactose-1-P uridylyltransferase.

Impairment of the human enzyme galactose-1-P uridylyltransferase (hGALT) results in the potentially lethal disorder, galactosemia. One of the fundamental questions with regard to this dimeric enzyme involves the possible influence of patient mutations on heterodimer formation and activity. Indeed, considering that many if not most galactosemia patients are compound heterozygotes, this is an issue of clinical as well as basic science interest.