Notice: Identification of Human Cell Lines Project
Federal Register: Volume 77, Number 23 (Friday, February 3, 2012)
AGENCY: National Institute of Standards and Technology, Commerce.
SUMMARY: The National Institute of Standards and Technology (NIST)
Biochemical Science Division announces its intent to identify by short
tandem repeat (STR) profiling up to 1500 human cell line samples as
part of the Identification of Human Cell Lines Project. All data and
corresponding information will be posted in a publically held database
at the National Center For Biotechnology Information (NCBI).
DATES: On the first of each month beginning after February 3, 2012 NIST
will post the number of cell lines accepted on the NIST Applied
Genetics Group Web site at http://www.nist.gov/mml/biochemical/genetics/index.cfm.
Once the total number of accepted submissions has
reached 1400 cell lines, the next month will be the final month NIST
will accept submissions, with the total time for acceptance not to
exceed one year beyond February 3, 2012.
ADDRESSES: Hard copies of submissions must be submitted to the
attention of Margaret Kline at the National Institute of Standards and
Technology; 100 Bureau Drive, Stop 8314; Gaithersburg, MD 20899-8314.
Electronic submissions must be submitted to Margaret.Kline@nist.gov.
FOR FURTHER INFORMATION CONTACT: Margaret Kline via email at
Margaret.Kline@nist.gov or telephone (301) 975-3134.
Program Description: The National Institute of Standards and
Technology (NIST) Biochemical Science Division announces its intent to
unambiguously identify by short tandem repeat (STR) profiling up to
1500 human cell line samples as part of the Identification of Human
Cell Lines Project. All data and corresponding information will be
posted in a publically held database.
The use of misidentified cell lines in cancer and other biomedical
research continues to occur, resulting in the possibility that a
significant proportion of the literature describing studies employing
cell lines may be misleading or even false. The end result of this
unfortunate situation is that millions of dollars may be spent on
research using misidentified cell lines every year worldwide. This, in
turn, may delay discoveries and the effective translation of research
findings from the laboratory to the clinic or the market. Scientists
may believe or claim that they are working with cells derived from one
individual or animal species, only to eventually learn that the cells
were derived from a different individual or species. With the advent of
standardized, simple, and rapid methods for human cell line
authentication the identity of a cell line need no longer be in doubt.
NIST is undertaking this project to provide that cell line
Human cell lines submitted for identification as part of this
project will undergo STR profiling, a DNA profiling method that
examines/screens for STRs (DNA elements 2-6 bps long repeated in
tandem) in the human chromosomes, that has been shown to be not only
rapid and inexpensive, but also able to generate reproducible data in a
format suitable for use in a standard reference database. STR analysis
involves simultaneous amplification of eight STR markers (e.g., D5S818,
D13S317, D7S820, D16S539. vWA, THO1, TPOX, CSF1PO) and the amelogenin
gene for gender determination. For each STR marker used, the power of
discrimination improves by about an order of magnitude. Thus, with 8
STRs, random match probabilities on the order of 1 in 100 million are
expected between cell line DNA samples originating from unrelated
individuals. Each unique human cell line has a distinct DNA profile and
when the STR DNA fragment sizes are converted to numeric values, the
DNA profiles are readily compared among different laboratories. It
should be noted,
however, that STR profiling cannot detect interspecies cross-
contamination. For this reason, cell lines grown on non-human feeder
cells will not be accepted for this project.
The attributes of STR-profiling which have driven the selection of
this technology over other possible candidates for this project
include: (i) The ability to discriminate human cell lines to the
individual level upon evaluating a relatively limited number of allelic
markers; (ii) reproducibility of the endpoint across different
laboratories and therefore the feasibility of assembling and
maintaining a searchable and public (freely accessible) database for
authenticating established cell lines; (iii) the commercial
availability of STR-profiling kits, allowing individual laboratories to
bring this technology in-house; (iv) relatively low cost; (v) rapidity;
and (vi) reduced need for specialized technical expertise and/or
reagents, compared with many of the other authentication technologies.
Presently, cell line STR profiling appears to represent the greatest
value to the scientific community for authenticating human cell lines
unambiguously, quickly, and for the least expense.
There is a tremendous need for scientific researchers using cell
lines to know with confidence that the cells they are using are of the
desired origin. This interactive database will be used by the research
and development community to validate cell lines of interest. The
database will offer DNA profiles of commonly used standard cell lines,
primary, differentiating, and commonly used immortalized and
transformed cell lines, as donated by interested parties.
Furthermore, the database will allow disparate laboratories to
compare their lines, thereby facilitating the validation of
experimental data. Thus, the database will address the need for
investigators to know much more about the samples used in their
research, and will fulfill an overarching need of researchers to
characterize their substrates with an accepted standard.
The current databases for cell lines generated using various
numbers of STR loci will be useful as long as the new extended set of
STR loci include the current loci. Thus, the current database will not
be absolute and can be updated when existing cell lines are retyped as
a routine measure using the extended set of STR loci.
Information on cell lines in the database will include multiple
attributes of the cell lines (name and possible synonyms of cell line,
organism, tissue of origin, morphology, pathologic or disease-state,
hybrid or mixed culture, feeder cells, date of origin, etc), the STR
markers and procedures used in identification, the submitter and
appropriate links, other descriptive material, and the STR profile
(electropherogram) of the cell line.
Scientists at NIST will evaluate data from STR profiling as
described in Designation: ASN-0002 Authentication of Human Cell Lines:
Standardization of STR Profiling by NIST will make no conclusions
regarding uniqueness of cell line, whether the cell line matches
another cell line, whether the cell line is misidentified, cross-
contaminated, or genetically unstable.
Identification by STR profiling of human cell lines will be
provided by the Biochemical Science Division (BSD)/Material Measurement
Laboratory (MML)/NIST. This program is contingent upon the availability
of BSD/MML/NIST program funds, BSD/MML/NIST program objectives, and the
discretion of BSD/MML/NIST advisors. The timeline for completing the
STR profiling will be contingent on resources available.
NIST anticipates entering into a Materials Transfer Agreement with
each submitter. To obtain a copy of the NIST Materials Transfer
Agreement to be used for this project, please contact Margaret Kline,
whose contact information is given in the ADDRESSES section above.
Applicants who submit complete information about their cell lines
and who enter into a Material Transfer Agreement with NIST will be
eligible to participate in the Identification of Human Cell Lines
Project on a first-come, first served basis. Once the Material Transfer
Agreement is executed, institutions will have 30 business days to
submit the agreed-upon cell lines. Note that submitters must be willing
to have submitter information made public in the aforementioned
Submission Process: Submitters should contact Margaret Kline with a
list of proposed cell lines for identification. Each submitter may
submit up to 15 cell lines. Note that no cell lines grown on non-human
feeder cells will be accepted due to the possibility of contamination.
NIST will perform STR profiling of up to 1500 cell lines submitted with
complete information on a first-come, first-serve basis. As part of the
submission, the following information, using standard nomenclature,
should be included for each cell line or DNA extract, as applicable.
Please do not include any personally identifiable information regarding
the source of the cell lines.
Cell Line Name =
Tissue of Origin =
Pathologic or Disease-State =
Hybrid or Mixed Culture =
Feeder Cells (species):
Population Doubling Level (PDL):
Complete Growth Media:
Date of Origin/Date Established:
If DNA extracts are submitted, the following information is
Source of DNA:
Cell line or derivatives
DNA Isolation Method:
Other (Cellmark kit)
Method of DNA Quantitation:
Spectrophotometer (Nanodrop, etc.)
Amount of DNA Used for Analysis:
Other Characterization and Authentication Methods: (example:
cytogenetic analysis i.e. G-banding or SKY; Microarray analysis; SNP;
Other Characterization and Authentication Methods: provide
reference and data.
Are the cell lines genetically engineered? If yes, explain how.
Costs for shipping accepted cell lines to NIST are the
responsibility of the donating party, and will not be paid for by NIST.
Review and Selection Process: All submissions will be reviewed to
determine whether they are complete. All complete submissions will be
accepted based on date and time of receipt of submission. Up to 15 cell
lines per submitter or establishment will be accepted, with a final
limit of 1500 cell lines. No cell lines grown on non-human feeder cells
will be accepted due to the possibility of cross-species contamination.
Research Projects Involving Human Subjects, Human Tissue, Data or
Recordings Involving Human Subjects: NIST has determined that this
project does not include research involving human subjects that falls
under the Common Rule for the Protection of Human Subjects.
Paperwork Reduction Act: This notice contains collection of
information requirements subject to the Paperwork Reduction Act (PRA).
The collection of information has been approved by OMB under control
number 0693-0064, and completion of this information for a single cell
line is expected to take 2 hours and 30 minutes. Notwithstanding any
other provision of the law, no person is required to respond to, nor
shall any person be subject to a penalty for failure to comply with, a
collection of information, subject to the requirements of the PRA,
unless that collection of information displays a currently valid OMB
Dated: January 27, 2012.
Willie E. May,
Associate Director for Laboratory Programs.
[FR Doc. 2012-2459 Filed 2-2-12; 8:45 am]
BILLING CODE 3510-13-P