Genetic alternation in Peutz-Jeghers Syndrome (PJS) and its Diagnostic Method
Abstract
Peutz-Jegers Syndrome (PJS) autosomal dominant disorder characterized by melanin spots, colon polyps and increased risk of cancer, especially due to mucosal skin pigmentation of the red edges of the lips, and gastrointestinal hematogenous polyposis. PJS was first reported in 1895. PJS can caused with or without mutation. Polyps have also been seen in the ureter, airway body system, and gastrointestinal system. The most common location is jejunum. DBE is an enteroscopy technique that enables the evaluation and treatment of the small bowel. Cancers of the colon, stomach, small intestine, pancreas, breast, and other organs are more common in PJS patients. PJS has a strong link with several malignancies like adenoma malignum (ADM) and a rare ovary tumor called sex cord tumor with annular tubules (SCTATs) in female PJS patients.
Keywords:
Peutz-Jeghers Syndrome, intraoperative enteroscopy, dual-balloon enteroscopy
References
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3. Hutchinson J. Pigmentation of lips and mouth. Arch Surg (Lond). 1896; 7: 290.
4. Parikh SB, Parikh BJ, Prajapati HA, Shah CK, Shah NR. Case report Peutz-Jeghers syndrome. Gujarat Med J. 2013; 68: 106-108.
5. Wang Z, Chen Y, Wu B, Zheng H, He J, Jiang B. A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Chinese patients. BMC Med Gen. 2011; 12: 161.
6. Mehenni H, Gehrig C, Nezu JI, Oku A, Shimane M, Rossier C, Guex N, Blouin JL, Scott HS, Antonarakis SE. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Gen. 1998; 63: 1641-50.
7. Weng MT, Ni YH, Su YN, Wong JM, Wei SC. Clinical and genetic analysis of PeutzJeghers syndrome patients in Taiwan. J Formosan Med Assoc. 2010; 109: 354-61.
8. Volikos E, Robinson J, Aittomäki K, Mecklin JP, Järvinen H, Westerman AM, de Rooji FW, Vogel T, Moeslein G, Launonen V, Tomlinson IP. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Gen. 2006; 43: 18
9. Jeghers H. McKusick V, Katz K. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. New Engl J Med. 1949; 241: 993–1005.
10. Weber FP. Patches of deep pigmentation of oral mucous membrane not connected with Addison’s disease. Quart J Med. 1919; 12: 404.
11. Peutz J, Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Maandschr Geneesk. 1921; 10: 134–46.
12. Bruwer A, Bargen J, Kierland R. Surface pigmentation and generalized intestinal polyposis (Peutz-Jeghers syndrome). Proc Staff Meet Mayo Clin. 1954; 29: 168–71.
13. Reid J. Intestinal carcinoma in Peutz Jeghers syndrome. JAMA. 1974; 229: 833–4
14. Hearle N et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006; 12: 3209–15.
15. Hemminki A et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet. 1997;15(1):87–90.
16. Hemminki A et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998;391(6663):184–7.
17. Jenne DE et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38–43.
18. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, Brien TP, Bozzuto CD, Ooi D, Cantley LC, Yuan J. The Peutz-Jegher gene product LKB1 is a mediator of p53- dependent cell death. Mol Cell. 2001; 7: 1307-19.
19. Launonen V. Mutations in the human LKB1/STK11 gene. Human Mutation. 2005;26: 291-7.
20. Huang Z, Miao S, Wang L, Zhang P, Wu B, Wu J, Huang Y. Clinical characteristics and STK11 gene mutations in Chinese children with Peutz-Jeghers syndrome. BMC Gastroenterol. 2015; 15: 166.
21. Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Hirasawa A, Aoki D. Hereditary gynecological tumors associated with Peutz Jeghers syndrome. Oncology letters. 2013; 6: 1184-8.
22. McGarrity TA, Amos C. Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci. 2006; 63(18):2135-44.
23. Casey G et al. Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA. 2005; 293(7):799–809.
24. Hearle NC, et al. Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome. BMC Genomics. 2005;6(1):38.
25. Olschwang S, et al. Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J Med Genet. 1998;35(1):42–4.
26. Mehenni H et al. Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet. 1997;61(6):1327–34.
27. Hearle N et al. Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11- negative PJS cases. Genes Chromosomes Cancer. 2004;41(2):163–9.
28. Buchet-Poyau K et al. Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res. 2002;97(3–4):171–8.
29. Alhopuro P, et al. Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADalpha, and MO25alpha, in Peutz-Jeghers syndrome. Br J Cancer. 2005;92(6):1126–9.
30. Bartholomew LG, Dahlin DC, Waugh JM, Intestinal polyposis associated with mucocutaneous melanin pigmentation Peutz-Jeghers syndrome; review of literature and report of six cases with special reference to pathologic findings. Gastroenterology. 1957;32:434–51.
31. Jansen M et al. Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis. Gut. 2006;55(1):1–5.
32. Rebsdorf Pedersen I, et al. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish polyposis register. Int J Colorectal Dis. 1994;9(4):177–9.
33. Tomlinson IP, Houlston RS. Peutz-Jeghers syndrome. J Med Genet. 1997;34(12):1007–11.
34. Goldstein, S. A.; Hoffenberg, E. J. Peutz-Jegher Syndrome in Childhood. J. Pediatr. Gastroenterol. Nutr. 2013, 56(2):191–195.
35. Kopácová M, Bures J, Ferko A, Tachecí I, Rejchrt S. Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc. 2010; 24(8):1904-10.
36. Hearle N et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006; 12(10):3209–15.
37. Srivatsa PJ, Keeney GL, Podratz KC. Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz-Jeghers syndrome. Gynecol Oncol. 1994; 53(2):256–64.
38. Spigelman AD, Murday V, Phillips RK. Cancer and the Peutz-Jeghers syndrome. Gut. 1989; 30(11):1588–90.
39. Gilks CB et al. Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases. Am J Surg Pathol. 1989; 13(9):717–29.
40. Tsuruchi N et al. Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome. Gynecol Oncol. 1994; 54(2):232–6.
41. Okamoto Y, Tanaka YO, Nishida M, Tsunoda H, Yoshikawa H, Itai Y, MR Imaging of the Uterine Cervix: Imaging-Pathologic Correlation. RadioGraphics 2003, 23 (2): 425–445.
42. Ishii K, et al. A new diagnostic method for adenoma malignum and related lesions: latex agglutination test with a new monoclonal antibody, HIK1083. Clin Chim Acta. 2001; 312(1–2):231–3.
43. McCluggage WG. Endocervical glandular lesions: controversial aspects and ancillary techniques. J Clin Pathol. 2003; 56(3):164–73.
44. Tsuda H, et al. Reproducible and clinically meaningful differential diagnosis is possible between lobular endocervical glandular hyperplasia and ‘adenoma malignum’ based on common histopathological criteria. Pathol Int. 2005; 55(7):412–8.
45. Young RH, Scully RE. Ovarian sex cord-stromal tumors: recent progress. Int J Gynecol Pathol. 1982; 1(1):101–23.
46. Lele SM et al. Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz-Jeghers syndrome: a case report. Mod Pathol. 2000;13(4):466–70.
47. Rodu B, Martinez Jr MG. Peutz-Jeghers syndrome and cancer. Oral Surg Oral Med Oral Pathol. 1984; 58(5):584–8.
48. Gibbon DG. Conservative management of sex cord tumors with annular tubules of the ovary in women with Peutz-Jeghers syndrome. J Pediatr Hematol Oncol. 2005;27(11):630–2.
49. Ulbright TM, Amin MB, Young RH, Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am. J. Surg. Pathol. 2007;31(6):827–35.
50. Lefevre H, et al. Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor. Eur J Endocrinol. 2006;154(2):221–7.
51. Osorio JC, Castillo A, Epigenetic Mechanisms in Head and Neck Cancer. New Aspects in Molecular and Cellular Mechanisms of Human Carcinogenesis 2016. https://www.intechopen.com/chapters/48921
52. Kanherkar RR, Bhatia-Dey N, Csoka AB, Epigenetics across the human lifespan. Frontiers Cell Development Bio. 2014;2:49.
53. Weinhold B. Epigenetics: the science of change. Environmental health perspectives. 2006; 114(3): A160.
54. Rodenhiser D, Mann M, Epigenetics and human disease: translating basic biology into clinical applications. Canadian Medical Association Journal. 2006;174(3):341- 8
55. Williams SD, Hughes TE, Adler CJ, Brook AH, Townsend GC. Epigenetics: a new frontier in dentistry. Australian Dent. J. 2014; 59(s1):23-33.
56. http://www.abcam.com/epigenetics/histone-modifications-a-guide.
57. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell res. 2011; 21(3): 381.
58. Phillips T. Small non-coding RNA and gene expression. Nature Edu. 2008; 1(1):115.
59. Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA, Herman JG. Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene. 2000; 19(1):164.
2. Hosogi H, Nagayama S, Kawamura J, Koshiba Y, Nomura A, Itami A, Okabe H, Satoh S, Watanabe G, Sakai Y. Molecular insights into Peutz-Jeghers syndrome: two probands with a germline mutation of LKB1. J Gastroenterol. 2008; 43: 492-7.
3. Hutchinson J. Pigmentation of lips and mouth. Arch Surg (Lond). 1896; 7: 290.
4. Parikh SB, Parikh BJ, Prajapati HA, Shah CK, Shah NR. Case report Peutz-Jeghers syndrome. Gujarat Med J. 2013; 68: 106-108.
5. Wang Z, Chen Y, Wu B, Zheng H, He J, Jiang B. A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in Chinese patients. BMC Med Gen. 2011; 12: 161.
6. Mehenni H, Gehrig C, Nezu JI, Oku A, Shimane M, Rossier C, Guex N, Blouin JL, Scott HS, Antonarakis SE. Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Gen. 1998; 63: 1641-50.
7. Weng MT, Ni YH, Su YN, Wong JM, Wei SC. Clinical and genetic analysis of PeutzJeghers syndrome patients in Taiwan. J Formosan Med Assoc. 2010; 109: 354-61.
8. Volikos E, Robinson J, Aittomäki K, Mecklin JP, Järvinen H, Westerman AM, de Rooji FW, Vogel T, Moeslein G, Launonen V, Tomlinson IP. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Gen. 2006; 43: 18
9. Jeghers H. McKusick V, Katz K. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits. New Engl J Med. 1949; 241: 993–1005.
10. Weber FP. Patches of deep pigmentation of oral mucous membrane not connected with Addison’s disease. Quart J Med. 1919; 12: 404.
11. Peutz J, Very remarkable case of familial polyposis of mucous membrane of intestinal tract and nasopharynx accompanied by peculiar pigmentations of skin and mucous membrane. Nederl Maandschr Geneesk. 1921; 10: 134–46.
12. Bruwer A, Bargen J, Kierland R. Surface pigmentation and generalized intestinal polyposis (Peutz-Jeghers syndrome). Proc Staff Meet Mayo Clin. 1954; 29: 168–71.
13. Reid J. Intestinal carcinoma in Peutz Jeghers syndrome. JAMA. 1974; 229: 833–4
14. Hearle N et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006; 12: 3209–15.
15. Hemminki A et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet. 1997;15(1):87–90.
16. Hemminki A et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 1998;391(6663):184–7.
17. Jenne DE et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38–43.
18. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, Brien TP, Bozzuto CD, Ooi D, Cantley LC, Yuan J. The Peutz-Jegher gene product LKB1 is a mediator of p53- dependent cell death. Mol Cell. 2001; 7: 1307-19.
19. Launonen V. Mutations in the human LKB1/STK11 gene. Human Mutation. 2005;26: 291-7.
20. Huang Z, Miao S, Wang L, Zhang P, Wu B, Wu J, Huang Y. Clinical characteristics and STK11 gene mutations in Chinese children with Peutz-Jeghers syndrome. BMC Gastroenterol. 2015; 15: 166.
21. Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Hirasawa A, Aoki D. Hereditary gynecological tumors associated with Peutz Jeghers syndrome. Oncology letters. 2013; 6: 1184-8.
22. McGarrity TA, Amos C. Peutz-Jeghers syndrome: clinicopathology and molecular alterations. Cell Mol Life Sci. 2006; 63(18):2135-44.
23. Casey G et al. Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA. 2005; 293(7):799–809.
24. Hearle NC, et al. Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome. BMC Genomics. 2005;6(1):38.
25. Olschwang S, et al. Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J Med Genet. 1998;35(1):42–4.
26. Mehenni H et al. Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet. 1997;61(6):1327–34.
27. Hearle N et al. Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11- negative PJS cases. Genes Chromosomes Cancer. 2004;41(2):163–9.
28. Buchet-Poyau K et al. Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res. 2002;97(3–4):171–8.
29. Alhopuro P, et al. Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADalpha, and MO25alpha, in Peutz-Jeghers syndrome. Br J Cancer. 2005;92(6):1126–9.
30. Bartholomew LG, Dahlin DC, Waugh JM, Intestinal polyposis associated with mucocutaneous melanin pigmentation Peutz-Jeghers syndrome; review of literature and report of six cases with special reference to pathologic findings. Gastroenterology. 1957;32:434–51.
31. Jansen M et al. Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis. Gut. 2006;55(1):1–5.
32. Rebsdorf Pedersen I, et al. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish polyposis register. Int J Colorectal Dis. 1994;9(4):177–9.
33. Tomlinson IP, Houlston RS. Peutz-Jeghers syndrome. J Med Genet. 1997;34(12):1007–11.
34. Goldstein, S. A.; Hoffenberg, E. J. Peutz-Jegher Syndrome in Childhood. J. Pediatr. Gastroenterol. Nutr. 2013, 56(2):191–195.
35. Kopácová M, Bures J, Ferko A, Tachecí I, Rejchrt S. Comparison of intraoperative enteroscopy and double-balloon enteroscopy for the diagnosis and treatment of Peutz-Jeghers syndrome. Surg Endosc. 2010; 24(8):1904-10.
36. Hearle N et al. Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res. 2006; 12(10):3209–15.
37. Srivatsa PJ, Keeney GL, Podratz KC. Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz-Jeghers syndrome. Gynecol Oncol. 1994; 53(2):256–64.
38. Spigelman AD, Murday V, Phillips RK. Cancer and the Peutz-Jeghers syndrome. Gut. 1989; 30(11):1588–90.
39. Gilks CB et al. Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases. Am J Surg Pathol. 1989; 13(9):717–29.
40. Tsuruchi N et al. Adenoma malignum of the uterine cervix detected by imaging methods in a patient with Peutz-Jeghers syndrome. Gynecol Oncol. 1994; 54(2):232–6.
41. Okamoto Y, Tanaka YO, Nishida M, Tsunoda H, Yoshikawa H, Itai Y, MR Imaging of the Uterine Cervix: Imaging-Pathologic Correlation. RadioGraphics 2003, 23 (2): 425–445.
42. Ishii K, et al. A new diagnostic method for adenoma malignum and related lesions: latex agglutination test with a new monoclonal antibody, HIK1083. Clin Chim Acta. 2001; 312(1–2):231–3.
43. McCluggage WG. Endocervical glandular lesions: controversial aspects and ancillary techniques. J Clin Pathol. 2003; 56(3):164–73.
44. Tsuda H, et al. Reproducible and clinically meaningful differential diagnosis is possible between lobular endocervical glandular hyperplasia and ‘adenoma malignum’ based on common histopathological criteria. Pathol Int. 2005; 55(7):412–8.
45. Young RH, Scully RE. Ovarian sex cord-stromal tumors: recent progress. Int J Gynecol Pathol. 1982; 1(1):101–23.
46. Lele SM et al. Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz-Jeghers syndrome: a case report. Mod Pathol. 2000;13(4):466–70.
47. Rodu B, Martinez Jr MG. Peutz-Jeghers syndrome and cancer. Oral Surg Oral Med Oral Pathol. 1984; 58(5):584–8.
48. Gibbon DG. Conservative management of sex cord tumors with annular tubules of the ovary in women with Peutz-Jeghers syndrome. J Pediatr Hematol Oncol. 2005;27(11):630–2.
49. Ulbright TM, Amin MB, Young RH, Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am. J. Surg. Pathol. 2007;31(6):827–35.
50. Lefevre H, et al. Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor. Eur J Endocrinol. 2006;154(2):221–7.
51. Osorio JC, Castillo A, Epigenetic Mechanisms in Head and Neck Cancer. New Aspects in Molecular and Cellular Mechanisms of Human Carcinogenesis 2016. https://www.intechopen.com/chapters/48921
52. Kanherkar RR, Bhatia-Dey N, Csoka AB, Epigenetics across the human lifespan. Frontiers Cell Development Bio. 2014;2:49.
53. Weinhold B. Epigenetics: the science of change. Environmental health perspectives. 2006; 114(3): A160.
54. Rodenhiser D, Mann M, Epigenetics and human disease: translating basic biology into clinical applications. Canadian Medical Association Journal. 2006;174(3):341- 8
55. Williams SD, Hughes TE, Adler CJ, Brook AH, Townsend GC. Epigenetics: a new frontier in dentistry. Australian Dent. J. 2014; 59(s1):23-33.
56. http://www.abcam.com/epigenetics/histone-modifications-a-guide.
57. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell res. 2011; 21(3): 381.
58. Phillips T. Small non-coding RNA and gene expression. Nature Edu. 2008; 1(1):115.
59. Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA, Herman JG. Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene. 2000; 19(1):164.
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How to Cite
Kunal Verma, and Shobhit Kumar. “Genetic Alternation in Peutz-Jeghers Syndrome (PJS) and Its Diagnostic Method”. Current Research in Pharmaceutical Sciences, Vol. 12, no. 2, July 2022, pp. 74-82, doi:10.24092/CRPS.2022.120201.
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