C.C. Lin

Fragile sites and structural rearrangements in cancer

SummaryWe retracted information from a computerized databank which contains the cytogenetic findings of 17,000 patients with leukemia and lymphoma. Cytogenetic data from patients with solid tumors were compiled from Dr. Mitelmans catalogue on “Chromosome aberrations in cancer”. We compared the observed distribution of breaks in chromosome bands involved in structural rearrangements with the random distribution of breaks generated by Monte Carlo simulation and showed that a majority but not all of the bands known to contain a fragile site are involved in structural aberrations in cancer and that some of them are associated with specific chromosome structural changes in specific types of cancer.

High-resolution chromosomal localization of the β-gene of the human β-globin gene complex by in situ hybridization

A 4.4-kb PstI fragment containing the entire beta-gene of the human beta-globin gene cluster plus both 5- and 3-flanking sequences was used as a probe to study the chromosomal localization of the beta-gene by in situ hybridization. Using random oligonucleotides as primers, the beta-gene DNA was 3H-labeled with the large fragment of DNA polymerase I (Klenow fragment) to a specific activity of 1.2 X 10(8) cpm/micrograms. Almost 80% of hybridization grains observed were located on the distal short arm of chromosome 11. High-resolution chromosome analysis suggests a more precise location of the beta-gene to region 11p15.4----p15.5.

4;11 translocation-associated acute leukemia: A comprehensive analysis☆

A girl with common acute lymphoblastic leukemia associated with t(4;11)(q21;q23) is presented. The physical examination revealed hepatosplenomegaly, and the hematologic analysis showed a high count of white cells. Chemotherapy induced a complete remission (CR), and the patient is still in CR (8 months). At the present time, 43 cases (including ours) of acute leukemia with t(4;11) have been published. This disease more often affects children and women than adult men and is characterized by a high blood white cell count and a short survival. The t(4;11)-associated acute leukemia is a heterogeneous group, including acute undifferentiated leukemia, acute undifferentiated lymphoblastic leukemia, and common acute lymphoblastic leukemia.

Cytogenetic analysis of great horned owls (Bubo virginianus).

A chromosome analysis of seven great honored owls (Bubo virginianus, Gmelin) has been performed on peripheral lymphocytes. The modal chromosome number was found to be 2n = 82. Measurements of relative lengths and arm ratios of the macrochromosomes were made. All chromosomes contain a region of constitutive heterochromatin in a centromeric location, with the W chromosome being composed almost entirely of this material. Chromosome replication, as demonstrated by the BudR-acridine orange method, showed synchronous replication of the two Z chromosomes of the male and late replication of the W chromosome of the female. In this species, functional regions of nucleolar organization appear to be localized to the microchromosomes.

Ultrastructural organization of double minute chromosomes and HSR regions in human colon carcinoma cells

The ultrastructural organization of double minute chromosomes (DMs) and marker chromosomes displaying homogeneously staining regions (HSRs) have been investigated in two cell lines, COLO-320 DM and COLO-320 HSR, derived from a human colon carcinoma. Double minute chromosomes in the COLO-320 DM cell line vary in number from several to several hundred and in diameter from 0.5 to 2 micron. These chromosomes lack kinetochore structures which appear as discrete electron dense plates on the centromeric chromosomes. The DMs are composed of regularly arranged nucleosome-containing fibers. These are folded to form 30 nm fibers which extend as loops from the central portion of the chromosome. In COLO-320 HSR, a majority of cells contain a single submetacentric HSR marker chromosome with HSR regions in both chromosome arms. The HSR chromosome appears structurally analogous in EM preparations to the other centromeric chromosomes of the karyotype.

The occurrence of the 15;17 translocation in acute promyelocytic leukemia

For many years, acute promyelocytic leukemia (APL) has been associated with the 15;17 translocation. However, questions concerning an eventual geographic distribution have been raised by the Second and Fourth International Workshops on Chromosomes in Leukemia. Using a statistical approach, we showed that, even if the techniques of processing play an important role in detecting the 15;17 translocation, a geographic distribution exists, which is difficult to explain. Finally, we discuss the possible role of c-erb A1 in acute promyelocytic leukemia.

A case of acute lymphoblastic leukemia with t(10;19)(q26;q13)

We report a patient with non-B non-T acute lymphoblastic leukemia (ALL) who has translocation t(10;19)(q26;q13), which has not been reported previously. A brief review of the translocations involving chromosome #19 in ALL is also presented.