Joseph R. Testa

The human calcitonin gene is located on the short ARM of chromosome 11

By molecular hybridization of human calcitonin cDNA probes to DNA from human-rodent hybrid cells containing identified human chromosomes, we have mapped the human calcitonin gene to the short arm of chromosome 11. This location has been confirmed by in situ hybridization, which further localized the calcitonin gene to region 11p13-15. The significance of this region regarding gene linkage and possible markers for inherited cancers is discussed.

Cytogenetic studies of a human medullary thyroid carcinoma cell line

Detailed karyotypic analyses were performed on early and late passages of the TT cell line derived from malignant cells of a patient with the sporadic form of medullary thyroid carcinoma. Most of the cells examined were hypodiploid with a modal chromosome number of 43. The cells have a complex karyotype with ten rearranged chromosomes found in early passages and 12 rearranged chromosomes in late passages. The karyotypic pattern was relatively stable with continued in vitro culture, and consistent alterations involved chromosomes X, #1, #3, #5, #7, #8, #9, #10, #11, #12, and #14. Rearrangements of chromosome #11 are of particular interest, because the gene for calcitonin, the polypeptide hormone marker for medullary thyroid carcinoma resides on this chromosome. In early passages, one #11 contained an insertion within band q13, and this abnormality was retained in late passages. In late passage cells the other #11 homolog developed a deletion of part of the short arm, which involves the calcitonin gene region. We were unable to detect any deletion of chromosome band 20p12, previously reported by other investigators to occur in the germ line of patients with the hereditary form of medullary thyroid carcinoma.

Isochromosome (8q) in four patients with adenocarcinoma of the lung

We report an isochromosome, i(8q), in combination with many other cytogenetic changes in tumor cells from four patients with lung cancer. In each case, the tumor subtype was adenocarcinoma. This isochromosome has not been identified in primary tumors from patients with other histological types of lung cancer. Among the few previously reported cytogenetic analyses of pulmonary adenocarcinomas, i(8q) has been observed in four additional patients. Therefore, i(8q) represents a recurring change in this specific type of lung cancer. In addition to i(8q), tumor cells from each of our four patients had different abnormalities of 17p, and two patients had alterations of 3p as well.

Clinical and cytogenetic features of familial erythroleukaemia

A family is described in which six members developed acute nonlymphocytic leukaemia (ANLL) over the past 1 5 years, all morphologically FAB M6. Five affected individuals (ages 54‐73) are members of a single sibship, the sixth (age 31) was the son of one of the affected sibs. The family lives in a rural area, and no environmental hazard has been identified. One of the six patients never resided in the same geographic area as the others. Three patients with leukaemia died without chemotherapy, two died shortly after the initiation of chemotherapy and the most recent patient never achieved remission, surviving 10 months. Bone marrow specimens from the two most recent patients were analysed for cytogenetic abnormalities using chromosome banding techniques. In addition, skin fibroblasts were examined in a single patient. The fibroblasts had a normal karyotype. Bone marrow cells from both patients had complex abnormalities. Some similarities were observed, including: (1) hypodiploidy; (2) loss of one chromosome 20; (3) the presence of multiple marker chromosomes. In each case one marker appeared to involve the‘missing’no. 20 with an alteration of the long arm—loss (20q —) in one patient and gain (20q +) in the other. Peripheral blood lymphocytes were grown in folate deficient medium, but no evidence for folate sensitive fragile sites was found. Marrow chromosomes from a third leukaemic sibling were examined without banding techniques in 1976 and the karyotype was 45.XY, — 18, — F(19 or 20), ‐I‐marker. No specific cytogenetic finding was common to the three patients studied except for the loss of an F group chromosome. This family is unique in the literature with six cases of familial leukaemia of the same morphologic subtype, and the cytogenetic findings suggest that loss or rearrangement of part of the long arm of a single chromosome 20 may have occurred in each of the three patients examined.