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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