Skip to main content
SpringerLink
Log in

Loss of heterozygosity at 19p13.2 and 2q21 in tumours from familial clusters of non-medullary thyroid carcinoma

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

Linkage studies have identified susceptibility loci for familial nonmedullary thyroid cancer (FNMTC), with and without cell oxyphilia, at chromosomal regions 19p13.2 and 2q21. There are few genetic analyses of FNMTC tumours reported at the present time and the eventual gene involved was not identified yet. The aim of this study was to assess the occurrence of loss of heterozygosity (LOH) at these loci in the tumours from familial clusters of NMTC. We have analysed LOH in 14 tumours from 9 two-case familial clusters of NMTC. Using paired blood (normal) and tumour DNA samples, we have genotyped ten microsatellite and one SNP markers throughout 19p13.2 and fourteen microsatellite markers at 2q21. Overall, eight (57%) and two (14%) out of the fourteen tumours analysed exhibited LOH at 19p13.2 and 2q21, respectively. In two families (22%), LOH for the same markers was demonstrable in the tumours of the two members of the same family. In one family (11%) LOH was demonstrable at both loci analysed. In four two-case familial clusters (44%), LOH at the 19p13.2 locus was found in only one of the tumour cases analysed. Detailed haplotype analysis showed that, in two families (22%), the pattern of LOH in tumours was consistent with selective retention of the haplotype shared by affected members. In the remaining cases, it was consistent with random allelic losses. In conclusion, we report the finding of LOH at the 19p13.2 and 2q21 loci in tumours from familial clusters of NMTC, providing evidence that inactivation of putative genes in these regions, acting as tumour-suppressors, may be involved in the development of tumours in the context of FNMTC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

BL:

BiLateral

CO:

Cell Oxyphilia

FA:

Follicular Adenoma

FFPE:

Formalin Fixed Paraffin Embedded Tissue

FNMTC:

Familial Non-Medullary Thyroid Carcinoma

FTC:

Follicular Thyroid Carcinoma

FV:

Follicular Variant of Papillary Thyroid Carcinoma

LOH:

Loss-of-heterozygosity

MF:

MultiFocal

MNG:

MultiNodular Goitre

N:

Normal DNA

NMTC:

Non-Medullary Thyroid Carcinoma

PBL:

Peripheral Blood Leukocyte

PTC:

Papillary Thyroid Carcinoma

SNP:

Single Nucleotide Polymorphism

SSCP:

Single Strand Conformation Polymorphism

T:

Tumour DNA

WLV:

Warthin-Like Variant

References

  1. Schlumberger MJ (1998) Papillary and follicular thyroid carcinoma. N Engl J Med 338:297–306

    Article  PubMed  CAS  Google Scholar 

  2. Stoffer SS, Van Dyke DL, Bach JV et al (1986) Familial papillary carcinoma of the thyroid. Am J Med Genet 25:775–782

    Article  PubMed  CAS  Google Scholar 

  3. Malchoff CD, Malchoff DM (2006) Familial nonmedullary thyroid carcinoma. Cancer Control 13:106–110

    PubMed  Google Scholar 

  4. Grossman RF, Tu SH, Duh QY, et al (1995) Familial nonmedullary thyroid cancer: an emerging entity that warrants aggressive treatment. Arch Surg 130:892–897

    PubMed  CAS  Google Scholar 

  5. Houlston RS, Stratton MR (1995) Genetics of non-medullary thyroid cancer. Q J Med 88:685–693

    CAS  Google Scholar 

  6. Malchoff CD, Malchoff DM (1999) Familial nonmedullary thyroid carcinoma. Semin Surg Oncol 16:16–18

    Article  PubMed  CAS  Google Scholar 

  7. Burgess JR, Duffield A, Wilkinson SJ et al (1997) Two families with an autossomal dominant inheritance pattern for papillary carcinoma of the thyroid. J Clin Endocrinol Metabol 82:345–348

    Article  CAS  Google Scholar 

  8. Hemminki K, Dong C (2000) Familial relationships in thyroid cancer by histopathological subtype. Int J Cancer 85:201–205

    PubMed  CAS  Google Scholar 

  9. Pal T, Vogl FD, Chappuis PO et al (2001) Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study. J Clin Endocrinol Metabol 86:5307–5312

    Article  CAS  Google Scholar 

  10. Frich L, Glattre E, Akslen LA (2001) Familial occurrence of nonmedullary thyroid cancer: a population-based study of 5673 first-degree relatives of thyroid cancer patients from Norway. Cancer Epidemiol Biomarkers Prev 10:113–117

    PubMed  CAS  Google Scholar 

  11. Hemminki K, Eng C, Chen B (2005) Familial risks for non-medullary thyroid cancer. J Clin Endocrinol Metabol 90:5747–5753

    Article  CAS  Google Scholar 

  12. Alsanea O, Wada N, Ain K et al (2000) Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series. Surgery 128:1043–1050

    Article  PubMed  CAS  Google Scholar 

  13. Uchino S, Noguchi S, Kawamoto H et al (2002) Familial nonmedullary thyroid carcinoma characterized by multifocality and a high recurrence rate in a large study population. World J Surg 26:897–902

    Article  PubMed  Google Scholar 

  14. Bignell GR, Canzian F, Shayeghi M et al (1997) Familial nontoxic multinodular goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer. Am J Hum Genet 61:1123–1130

    Article  PubMed  CAS  Google Scholar 

  15. Canzian F, Amati P, Harach HR, et al (1998) A gene predisposing to familial thyroid tumors with cell oxyphilia maps to chromomosome 19p132. Am J Hum Genet 63:1743–1748

    Article  PubMed  CAS  Google Scholar 

  16. Malchoff CD, Sarfarazi M, Tendler B et al (2000) Papillary thyroid carcinoma associated with papillary renal neoplasia: genetic linkage analysis of a distinct heritable tumor syndrome. J Clin Endocrinol Metabol 85:1758–1764

    Article  CAS  Google Scholar 

  17. McKay JD, Lesueur F, Jonard L et al (2001) Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21. Am J Hum Genet 69:440–446

    Article  PubMed  CAS  Google Scholar 

  18. Bevan S, Pal T, Greenberg CR et al (2001) A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: confirmation of linkage to TCO1. J Clin Endocrinol Metabol 86:3701–3704

    Article  CAS  Google Scholar 

  19. McKay JD, Thompson D, Lesueur F et al (2004) Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer. J Med Genet 41:407–412

    Article  PubMed  CAS  Google Scholar 

  20. Bonora E, Evangelisti C, Bonichon F et al (2006) Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas. Br J Cancer 11:1529–1536

    Article  Google Scholar 

  21. Musholt TJ, Musholt PB, Petrich T et al (2000) Familial papillary thyroid carcinoma: genetics, criteria for diagnosis, clinical features, and surgical treatment. World J Surg 24:1409–1417

    Article  PubMed  CAS  Google Scholar 

  22. Vasen HF, Mecklin JP, Khan PM, Lynch HT (1991) The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34:424–425

    Article  PubMed  CAS  Google Scholar 

  23. Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36:873–880

    PubMed  CAS  Google Scholar 

  24. Stankov K, Pastore A, Toschi L et al (2004) Allelic loss at chromosomes 2q21 and 19p13.2 in oxyphilic thyroid tumours. Int J Cancer 111:463–467

    Article  PubMed  CAS  Google Scholar 

  25. Charkes ND (2006) On the prevalence of familial nonmedullary thyroid cancer in multiply affected kindreds. Thyroid 16:181–186

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the financial support for this work by grants awarded by the “Edward Limbert Prize for Thyroid Pathology” of the Portuguese Society of Endocrinology Diabetes and Metabolism (SPEDM), and the funding from the Portuguese Ministry of Health (“Comissão de Fomento da Investigação em Cuidados de Saúde”). We thank all patients and family members that have participated in this study. We thank Dr. Maria Madalena Barroso, MD and Dr. Leonor Gomes, MD (University Hospitals of Coimbra), Dr. Lígia Prado e Castro, MD (Hospital Centre of Coimbra) and Dr. Teresa Carvalho, MD (Hospital of Viseu) for providing FFPE tissue and clinical information on some of the patients included in this study.

Author information

Authors and Affiliations

  1. Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, Avenida Bissaya Barreto, 98, 3000-075, Coimbra, Portugal

    Hugo João Prazeres & Teresa C. Martins

  2. Medical Faculty of the University of Porto, Porto, Portugal

    Hugo João Prazeres & Paula Soares

  3. Endocrinology Service, Portuguese Institute of Oncology of Coimbra FG, EPE, Coimbra, Portugal

    Fernando Rodrigues, Plamen Naidenov & Beatriz Campos

  4. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

    Paula Soares

  5. Laboratory of Histopathology, Portuguese Institute of Oncology of Coimbra FG, EPE, Coimbra, Portugal

    Paulo Figueiredo & Manuela Lacerda

  6. Centre of Neurosciences of Coimbra, Coimbra, Portugal

    Teresa C. Martins

Authors
  1. Hugo João Prazeres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando Rodrigues
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paula Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Plamen Naidenov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paulo Figueiredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beatriz Campos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manuela Lacerda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Teresa C. Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hugo João Prazeres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prazeres, H.J., Rodrigues, F., Soares, P. et al. Loss of heterozygosity at 19p13.2 and 2q21 in tumours from familial clusters of non-medullary thyroid carcinoma. Familial Cancer 7, 141–149 (2008). https://doi.org/10.1007/s10689-007-9160-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-007-9160-x

Keywords

Search

Navigation