22

lung cancer cell line (H378) with no detec-

table expression of c-myc. We compared the

chromatin structure of m-myc in H82 to t_hat

in H378 using DNase I sensitivity and DNA

methylation patterns. DNase I hypersen-

sitivity sites were identical in H82 and

H378 and were similar to the pattern seen in

a B-lymphoblastoid cell line, despite exten-

sive amplification of c-myc in H82. Methyla-

tion patterns were also very similar in H82

and H378, with hypomethylation or partial

methylation at the c-myc coding regions and

the flanking 5' sequences, despite the ab-

sence of detectable c-myc expression in

H378. Therefore, the predominant chromatin

structural patterns do not appear to corre-

late with observed differences in gene ex-

pression. In addition, these studies

demonstrate that the patterns of DNase I hy-

persensitivity and of methylation can remain

intact during a 40- to 50-fold gene

amplification, as observed for the c-myc

gene in H82.

Genetic Predisposition to Htmmn Lung Cancer.

Heighway, J., Thatcher, N., Cerny, T., Has-

leton, P.S. Department of Cell Biology,

Paterson Laboratories, Manchester, U.K. Br.

J. Cancer 53: 453-457, 1986.

The influence of polymorphic variants

of the human c-Ha-ras gene on predisposition

to lung cancer has been investigated. The

b,~n c-Ha-ras gene has been shown to reside

on a polymorphic BamHl restriction fragment.

This restriction fragment length polymor-

phism (RFLP) results from variation in the

size of a region of repetitive DNA 3' to the

gene. An attempt has been made to charac-

terise and compare the c-Ha-ras RFLP's in a

normal population and in a group of cancer

patients. DNA was extracted from the white

blood cells of i01 normal donors and four

common Ha-ras alleles identified, with oc-

casion~l rare alleles of various sizes. The

allele frequencies were examined in 132 lung

cancer patients, comprising 66 individuals

with small cell carcinoma of the lung (SCCL)

and 66 with non-small cell carcinoma of the

lung (non-SCCL). An abnormal allele dis-

tribution was found in individuals with non-

SCCL compared to both control and SCCL

values, suggesting a degree of genetic pre-

disposition to non-SCCL. In addition,

analysis of the Ha-ras RFLP's in solid lung

tumour samples inferred a deletion of

material from the short arm of chromosome ii

in two of 16 informative samples.

H,m~n Small-Cell Lung Cancers Show

Amplification and Expression of the N-myc

Gene.

Nau, M.M., Brooks, B.J. Jr., Carney, D.N. et

al. National Cancer Institute-Navy Medical

Oncology Branch, National Cancer Institute,

National Institutes of Health and Naval

Hospital, Bethesda, MD 20814-2015, U.S.A.

Proc. Natl. Acad. Sci. U.S.A. 83: 1092-1096,

1986.

We have found that 6 of 31 indepen-

dently derived human small-cell lung cancer

(SCLC) cell lines have 5- to 170-fold

amplified N-myc gene sequences. The

amplification is seen with probes from two

separate exons of N-myc, which are

homologous to either the second or the third

exon of the c-myc gene. Amplified N-myc

sequences were found in a tumor cell line

started prior to chemotherapy, in SCLC tumor

samples harvested directly from tumor metas-

tases at autopsy, and from a resected

primary lung cancer. Several N-myc-amplified

tumor cell lines also exhibited N-myc

hybridizing fragments not in the germ-line

position. In one patient's tumor, an addi-

tional amplified N-myc DNA fragment was ob-

served and this fragment was heterogenously

distributed in liver metastases. In contrast

to SCLC with neuronendocrine properties, no

non-small-cell lung cancer lines examined

were found to have N-myc amplification.

Fragments encoding two N-myc exons also

detect increased amounts of a 3-l-kilobase

N-myc mRNA in N-myc-amplified SCLC lines and

in one cell line that does not show N-myc

gene amplification. Both DNA and RNA

hybridization experiments show that in any

one SCLC cell line, only one myc-related

gene is amplified and expressed. We conclude

that N-myc amplification is both common and

potentially significant in the tumorigenesis

or tumor progression of SCLC.

Changes in the Phenotype of Human Small Cell

Lung Cancer Cell Lines after Transfection

and Expression of the C-myc Proto-Oncogene.

Johnson, B.E., Battey, J., Linnoila, I. et

al. National Cancer Institute-Navy Medical

Oncology Branch, Naval Hospital, Bethesda,

MD 20817, U.S.A.J. Clin. Invest. 78: 525-

532, 1986.

Small cell lung cancer growing in cell

culture possesses biologic properties that

allow classification into two categories:

classic and variant. Compared with classic

small cell lung cancer cell lines, variant