# LINKAGE ANALYSES IN MULTIPLE ENDOCRINE NEOPLASIA

> **NIH NIH R01** · YALE UNIVERSITY · 1993 · $271,431

## Abstract

The locus for multiple endocrine neoplasia, type 2A (MEN-2A), a dominantly
inherited cancer syndrome, has been mapped to the pericentromeric region
of chromosome 10.  The MEN-2A syndrome involves medullary thyroid carcinoma
(MTC), pheochromocytoma (PHEO), and hyperparathyroidism.  Two other related
inherited cancer syndromes, MEN-2B and MTC without PHEOS, also map to the
same region of chromosome 10.  The highly informative markers that are
close to and flank the MEN2A locus allow most family members in MEN-2A
kindreds to be identified as carriers or non-carriers with high
probabilities.  This is a significant advance since the ability to identify
presymptomatic carriers allows much more effective biochemical screening
for early signs of malignancy and prevention of metastasis.

During the previous grant period, we found the first evidence for MEN-2A
being on chromosome 10 and contributed significantly to its fine-scale
genetic mapping near the centromere of 10.  We have begun work to identify
the smallest molecular region that co-segregates with the abnormal allele
and then clone most of that region as the next step toward the positional
cloning of the MEN2A gene itself.  We propose continuing those efforts
using the resources we have assembled.

We will use a cloning strategy based on yeast artificial chromosomes using
many nucleation sites from which to clone and then walk.  There are many
built-in safeguards to overcome the inherent ambiguities in any one method
for mapping and ordering these clones.  Our hypothesis is that the MEN2A
region is about 4-6 Mb long and our existing 600+kb YAC contig, the
existing other nucleation sites, library resources (YAC and cosmid), and
mapping panels (meiotic and hybrid) are sufficient for most of that to be
cloned into ordered and integrated contigs without undue difficulty.
Identifying the MEN2A locus itself is more problematic, but the combination
of approaches available, including a new PCR-based method to enrich for all
cDNAs in a large genomic fragment, has a high probability of yielding the
locus.

## Key facts

- **NIH application ID:** 3170111
- **Project number:** 5R01CA032066-10
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** Kenneth K. KIDD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $271,431
- **Award type:** 5
- **Project period:** 1983-06-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170111

## Citation

> US National Institutes of Health, RePORTER application 3170111, LINKAGE ANALYSES IN MULTIPLE ENDOCRINE NEOPLASIA (5R01CA032066-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170111. Licensed CC0.

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